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BIOCHEMISTRY (236 journals)                  1 2 | Last

Showing 1 - 200 of 236 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 2)
ACS Central Science     Open Access   (Followers: 8)
ACS Chemical Biology     Full-text available via subscription   (Followers: 260)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 18)
Acta Biochimica Polonica     Open Access  
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 9)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 8)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 10)
Advances in Biological Chemistry     Open Access   (Followers: 7)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
African Journal of Biochemistry Research     Open Access   (Followers: 1)
African Journal of Chemical Education     Open Access   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
American Journal of Biochemistry     Open Access   (Followers: 9)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 67)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 15)
American Journal of Polymer Science     Open Access   (Followers: 26)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical and Bioanalytical Chemistry Research     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 166)
Angiogenesis     Hybrid Journal   (Followers: 3)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 55)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 44)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 20)
Archives of Insect Biochemistry and Physiology     Hybrid Journal  
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 3)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 22)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 4)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 15)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 25)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 4)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 313)
Biochemistry & Pharmacology : Open Access     Open Access   (Followers: 3)
Biochemistry & Physiology : Open Access     Open Access  
Biochemistry (Moscow)     Hybrid Journal   (Followers: 4)
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology     Hybrid Journal   (Followers: 3)
Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry     Hybrid Journal   (Followers: 3)
Biochemistry and Biophysics Reports     Open Access  
Biochemistry and Cell Biology     Hybrid Journal   (Followers: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6)
Biochemistry and Molecular Biology of Fishes     Full-text available via subscription   (Followers: 1)
Biochemistry Research International     Open Access   (Followers: 6)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 7)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 14)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 9)
Biochimie     Hybrid Journal   (Followers: 7)
Biochimie Open     Open Access  
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 30)
BioDrugs     Full-text available via subscription   (Followers: 7)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 11)
Biogeochemistry     Hybrid Journal   (Followers: 14)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 22)
Biomaterials Research     Open Access   (Followers: 4)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Hybrid Journal   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 24)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45)
Bitácora Digital     Open Access  
BMC Biochemistry     Open Access   (Followers: 14)
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca : Food Science and Technology     Open Access  
Carbohydrate Polymers     Hybrid Journal   (Followers: 8)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 6)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 6)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
ChemBioChem     Hybrid Journal   (Followers: 7)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 20)
Chemical Engineering Journal     Hybrid Journal   (Followers: 46)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Open Access   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 3)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 6)
Chemistry & Biology     Full-text available via subscription   (Followers: 30)
Chemistry and Ecology     Hybrid Journal  
ChemTexts     Hybrid Journal  
Clinica Chimica Acta     Hybrid Journal   (Followers: 33)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 18)
Clinical Chemistry     Full-text available via subscription   (Followers: 68)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 61)
Clinical Lipidology     Full-text available via subscription   (Followers: 1)
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 4)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 1)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 7)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 2)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 12)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 16)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 28)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 6)
DNA Barcodes     Open Access  
Doklady Biochemistry and Biophysics     Hybrid Journal   (Followers: 1)
Doklady Chemistry     Hybrid Journal  
Egyptian Journal of Biochemistry and Molecular Biology     Full-text available via subscription  
FABICIB     Open Access  
FEBS Letters     Hybrid Journal   (Followers: 56)
FEBS Open Bio     Open Access   (Followers: 3)
Fish Physiology and Biochemistry     Hybrid Journal   (Followers: 4)
Food & Function     Full-text available via subscription   (Followers: 5)
Foundations of Modern Biochemistry     Full-text available via subscription  
Free Radicals and Antioxidants     Full-text available via subscription   (Followers: 4)
Frontiers in Molecular Biosciences     Open Access   (Followers: 2)
Frontiers in Natural Product Chemistry     Hybrid Journal  
Global Biogeochemical Cycles     Full-text available via subscription   (Followers: 15)
Green Chemistry     Full-text available via subscription   (Followers: 11)
Histochemistry and Cell Biology     Hybrid Journal   (Followers: 5)
Indian Journal of Biochemistry and Biophysics (IJBB)     Open Access   (Followers: 3)
Indian Journal of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Indonesian Biomedical Journal     Open Access  
Insect Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 3)
International Journal of Biochemistry & Cell Biology     Hybrid Journal   (Followers: 8)
International Journal of Biochemistry and Biophysics     Open Access   (Followers: 1)
International Journal of Biological Chemistry     Open Access   (Followers: 4)
International Journal of Biomedical Nanoscience and Nanotechnology     Hybrid Journal   (Followers: 6)
International Journal of Food Contamination     Open Access  
International Journal of Plant Physiology and Biochemistry     Open Access   (Followers: 1)
International Journal of Plant Research     Open Access   (Followers: 3)
International Journal of Secondary Metabolite     Open Access   (Followers: 1)
Invertebrate Immunity     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 4)
Journal of Microbial & Biochemical Technology     Open Access   (Followers: 2)
Journal of Applied Biology & Biotechnology     Open Access   (Followers: 2)
Journal of Bioactive and Compatible Polymers     Hybrid Journal   (Followers: 3)
Journal of Biochemistry     Hybrid Journal   (Followers: 43)
Journal of Biochemistry and Molecular Biology Research     Open Access  
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 205)
Journal of Biomaterials Science, Polymer Edition     Hybrid Journal   (Followers: 9)
Journal of Carbohydrate Chemistry     Hybrid Journal   (Followers: 7)
Journal of Cellular Biochemistry     Hybrid Journal   (Followers: 5)
Journal of Chemical Biology     Hybrid Journal   (Followers: 3)
Journal of Chemical Neuroanatomy     Hybrid Journal  
Journal of Clinical Lipidology     Hybrid Journal   (Followers: 2)
Journal of Comparative Physiology B : Biochemical, Systemic, and Environmental Physiology     Hybrid Journal   (Followers: 4)
Journal of Drug Discovery and Therapeutics     Open Access  
Journal of Enzyme Inhibition and Medicinal Chemistry     Open Access   (Followers: 3)
Journal of Evolutionary Biochemistry and Physiology     Hybrid Journal  
Journal of Food and Drug Analysis     Open Access  
Journal of Forensic Toxicology and Pharmacology     Hybrid Journal   (Followers: 4)
Journal of Inborn Errors of Metabolism and Screening     Open Access  
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 7)
Journal of Medical and Biomedical Sciences     Open Access  
Journal of Medical Biochemistry     Open Access   (Followers: 4)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Molecular Biochemistry     Open Access   (Followers: 3)
Journal of Molecular Diagnostics     Hybrid Journal   (Followers: 6)
Journal of Neurochemistry     Hybrid Journal   (Followers: 4)
Journal of Nutritional Biochemistry     Hybrid Journal   (Followers: 7)
Journal of Pediatric Biochemistry     Hybrid Journal   (Followers: 1)
Journal of Peptide Science     Hybrid Journal   (Followers: 23)
Journal of Photochemistry and Photobiology B: Biology     Hybrid Journal   (Followers: 3)
Journal of Physiobiochemical Metabolism     Hybrid Journal   (Followers: 1)
Journal of Physiology and Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Plant Biochemistry and Biotechnology     Hybrid Journal   (Followers: 7)
Journal of Steroid Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Journal of Virology & Antiviral Research     Hybrid Journal   (Followers: 5)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 10)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Lab on a Chip     Full-text available via subscription   (Followers: 36)
Marine Chemistry     Hybrid Journal   (Followers: 6)
Methods in Enzymology     Full-text available via subscription   (Followers: 11)
Molecular and Biochemical Parasitology     Hybrid Journal   (Followers: 2)
Molecular and Cellular Biochemistry     Hybrid Journal   (Followers: 6)
Molecular Aspects of Medicine     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 6)
Molecular inhibitors in targeted therapy     Open Access  
Moscow University Chemistry Bulletin     Hybrid Journal   (Followers: 1)
Mycologia     Hybrid Journal  
Mycology : An International Journal on Fungal Biology     Hybrid Journal   (Followers: 5)
Natural Products and Bioprospecting     Open Access   (Followers: 2)
Nature Chemical Biology     Full-text available via subscription   (Followers: 73)
Nature Communications     Open Access   (Followers: 201)
Neurosignals     Open Access  
NOVA     Open Access  
Novelty in Biomedicine     Open Access  
OA Biochemistry     Open Access   (Followers: 1)
OA Inflammation     Open Access  
Ocean Acidification     Open Access   (Followers: 4)
Organic & Biomolecular Chemistry     Full-text available via subscription   (Followers: 87)

        1 2 | Last

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.478]   [H-I: 138]   [20 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [3049 journals]
  • Eucalyptus globulus extract protects against UVB-induced photoaging by
           enhancing collagen synthesis via regulation of TGF-β/Smad signals and
           attenuation of AP-1
    • Authors: Bom Park; Eunson Hwang; Seul A. Seo; Jin-Gyeong Cho; Jung-Eun Yang; Tae-Hoo Yi
      Pages: 31 - 39
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Bom Park, Eunson Hwang, Seul A. Seo, Jin-Gyeong Cho, Jung-Eun Yang, Tae-Hoo Yi
      UV irradiation triggers the overproduction of matrix metalloproteinases and collagen degradation, which in turn causes increased pigmentation, dryness, and deep wrinkling of the skin. These chronic symptoms are collectively referred to as photoaging. Eucalyptus globulus is an evergreen tree that is widely used in cosmetics because of its antimicrobial activity. In this study, we investigated the protective effect of 50% ethanol extracts of Eucalyptus globulus on UV-induced photoaging in vitro and in vivo. Normal human dermal fibroblasts were treated with Eucalyptus globulus at concentrations ranging from 1 to 100 μg/mL after UVB or non-UVB irradiation. We found that Eucalyptus globulus suppressed the expression of MMPs and IL-6, but increased the expression of TGF-β1 and procollagen type 1. In addition, Eucalyptus globulus inhibited activation of the AP-1 transcription factor, an inducer of MMPs. Eucalyptus globulus was also found to regulate TGF-β/Smad signaling by reversing the activity of negative Smad regulators. Lastly, in vivo studies showed that topical application of Eucalyptus globulus on UVB-irradiated hairless mice reduced wrinkle formation and dryness by down-regulating MMP-1 and up-regulating expression of elastin, TGF-β1, and procollagen type 1. Taken together, these data suggest that Eucalyptus globulus may be a useful agent in cosmetic products.
      Graphical abstract image

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 637 (2017)
  • Cardiotonic actions of quercetin and its metabolite tamarixetin through a
           digitalis-like enhancement of Ca2+ transients
    • Authors: Kengo Hayamizu; Sachio Morimoto; Miki Nonaka; Sumio Hoka; Toshiyuki Sasaguri
      Pages: 40 - 47
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Kengo Hayamizu, Sachio Morimoto, Miki Nonaka, Sumio Hoka, Toshiyuki Sasaguri
      The plant-derived flavonoid, quercetin (QCT), has many biological actions, including cardioprotective actions, resulting from its antioxidant and anti-inflammatory effects. In this study, effects of QCT and its metabolites on the contraction and Ca2+ transients (CaT) of mouse single cardiomyocytes were simultaneously measured and compared with those of isoproterenol and digoxin. Furthermore, cardiac function and plasma concentrations were analyzed after bolus intravenous administration of QCT in mice. QCT and its metabolite, tamarixetin, as well as isoproterenol and digoxin, enhanced the contraction and CaT of cardiomyocytes. The inotropic action of isoproterenol was accompanied by an increase in the velocities of sarcomere shortening and relengthening and CaT decay through activation of cAMP-dependent protein kinase; however, no such lusitropic effects accompanied the inotropic action of QCT, tamarixetin or digoxin. Intravenous administration of QCT to mice resulted in a sustained increase in cardiac systolic function; QCT was rapidly metabolized to tamarixetin and its plasma concentration was maintained at high levels over a similar time frame as the enhancement of cardiac systolic function. These results suggest that QCT exerts a cardiotonic action in vivo at least, in part, through digitalis-like enhancement of CaT by itself and its metabolite tamarixetin.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 637 (2017)
  • MiR-429 regulates the metastasis and EMT of HCC cells through targeting
    • Authors: Hongyan Xue; Guo-Yan Tian
      Pages: 48 - 55
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Hongyan Xue, Guo-Yan Tian
      Accumulating documents have revealed that microRNAs (miRNAs) play critical roles in the development and progression of tumors. MiR-429 has been reported to be involved in regulating various cellular processes. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) still need to be further studied. The present study aimed to investigate the function of miR-429 in the progression of HCC. In terms of this paper, it was found that miR-429 was down-regulated in HCC tissues and cells. After being transfected with miR-429 mimics, miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429. Rescue assays further verified that the function of miR-429 in HCC cells was exerted through targeting RAB23. In general, it was concluded that the signal pathway miR-429/RAB23 might be a potential target for HCC treatment.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 637 (2017)
  • Naringin prevents bone loss in a rat model of type 1 Diabetes mellitus
    • Authors: M. Rivoira; V. Rodríguez; G. Picotto; R. Battaglino; N. Tolosa de Talamoni
      Pages: 56 - 63
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): M. Rivoira, V. Rodríguez, G. Picotto, R. Battaglino, N. Tolosa de Talamoni
      The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 637 (2017)
  • Atorvastatin affects negatively respiratory function of isolated
           endothelial mitochondria
    • Authors: Izabela Broniarek; Wieslawa Jarmuszkiewicz
      Pages: 64 - 72
      Abstract: Publication date: 1 January 2018
      Source:Archives of Biochemistry and Biophysics, Volume 637
      Author(s): Izabela Broniarek, Wieslawa Jarmuszkiewicz
      The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 637 (2017)
  • Effect of quercetin on cell protection via erythropoietin and cell injury
           of HepG2 cells
    • Authors: Kazuhiko Nishimura; Risa Matsumoto; Yuuki Yonezawa; Hiroshi Nakagawa
      Pages: 11 - 16
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Kazuhiko Nishimura, Risa Matsumoto, Yuuki Yonezawa, Hiroshi Nakagawa
      Quercetin is a flavonoid that has roles in both cytoprotection and cytotoxicity. The relation of queretin's cytoprotective and cytotoxic effects are unknown. Quercetin has been shown to induce expression of hypoxia-inducible factor, a protein that is known to regulate transcription of the erythropoietin (EPO) gene, and EPO is known to have a cytoprotective effect. This study used HepG2 cells to assess whether the cell-protective and/or cytotoxic roles of quercetin are mediated by promotion of EPO production. Increases in the levels of HIF-1α protein and EPO mRNA were quercetin concentration-dependent, with significant increases observed from 10 μM quercetin. Silencing of EPO expression by si-EPO RNA attenuated quercetin-induced cytoprotection against hydrogen peroxide toxicity. Cytotoxicity, evidenced by the induction of apoptosis, was significantly increased by exposure to 50 μM quercetin. Specifically, the levels of cleaved caspase-3 and Bax and the rate of cell death increased, and the level of Bcl-2 decreased, in cells treated with 50 μM quercetin. In contrast, exposure to 10 μM quercetin attenuated cisplatin-induced apoptosis. However, quercetin's ability to protect cells from cisplatin-induced apoptosis was eliminated when EPO expression was silenced using si-EPO RNA. Together, these results suggested that quercetin's cytoprotective effects in HepG2 cells are mediated via EPO production.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/
      Issue No: Vol. 636 (2017)
  • One single salt bridge explains the different cytolytic activities shown
           by actinoporins sticholysin I and II from the venom of Stichodactyla
    • Authors: Esperanza Rivera-de-Torre; Juan Palacios-Ortega; Sara García-Linares; José G. Gavilanes; Álvaro Martínez-del-Pozo
      Pages: 79 - 89
      Abstract: Publication date: Available online 11 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Esperanza Rivera-de-Torre, Juan Palacios-Ortega, Sara García-Linares, José G. Gavilanes, Álvaro Martínez-del-Pozo
      Sticholysins I and II (StnI and StnII), α-pore forming toxins from the sea anemone Stichodactyla helianthus, are water-soluble toxic proteins which upon interaction with lipid membranes of specific composition bind to the bilayer, extend and insert their N-terminal α-helix, and become oligomeric integral membrane structures. The result is a pore that leads to cell death by osmotic shock. StnI and StnII show 93% of sequence identity, but also different membrane pore-forming activities. The hydrophobicity profile along the first 18 residues revealed differences which were canceled by substituting StnI amino acids 2 and 9. Accordingly, the StnID9A mutant, and the corresponding StnIE2AD9A variant, showed enhanced hemolytic activity. They also revealed a key role for an exposed salt bridge between Asp9 and Lys68. This interaction is not possible in StnII but appears conserved in the other two well-characterized actinoporins, equinatoxin II and fragaceatoxin C. The StnII mutant A8D showed that this single replacement was enough to transform StnII into a version with impaired pore-forming activity. Overall, the results show the key importance of this salt bridge linking the N-terminal stretch to the β-sandwich core. A conclusion of general application for the understanding of salt bridges role in protein design, folding and stability.
      Graphical abstract image

      PubDate: 2017-11-15T16:22:32Z
      DOI: 10.1016/
      Issue No: Vol. 636 (2017)
  • Regulation of glutamate dehydrogenase (GDH) in response to whole body
           freezing in wood frog liver linked to differential acetylation and
    • Authors: Stuart R. Green; Kenneth B. Storey
      Pages: 90 - 99
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Stuart R. Green, Kenneth B. Storey
      Glutamate dehydrogenase (GDH) represents a critical enzyme catalyzing the reaction spanning amino acid catabolism, the Krebs cycle, and urea production in the wood frog. GDH breaks down glutamate and NAD+ to generate α-ketoglutaric acid (α-KG), NADH and ammonium that can be metabolized to form urea. Purification of GDH from control and frozen male wood frog livers was performed using a two-step column chromatography procedure with a cation exchange column and a GTP-agarose affinity column. Analysis of kinetic parameters of the purified GDH showed several notable differences between the control and stress. Under standard assay conditions, the affinity of GDH for its substrates was significantly higher for the freeze-exposed enzyme than for the control (glutamate Km: 41% decrease, NAD+ Km: 40% decrease). The maximal activity for the control enzyme was also noted to be lower than the frozen. This suggests that the frozen form of the GDH was activated relative to the control form. Western blot analysis of common posttranslational modifications indicated that the frozen enzyme had a lower degree of acetylation and ADP-ribosylation than its control counterpart. These results suggest that GDH is regulated in the wood frog liver by means of altering post-translational modifications in response to freezing.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 636 (2017)
  • Acetyl-CoA carboxylase from Escherichia coli exhibits a pronounced
           hysteresis when inhibited by palmitoyl-acyl carrier protein
    • Authors: Alexandra Evans; Wendy Ribble; Erin Schexnaydre; Grover L. Waldrop
      Pages: 100 - 109
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Alexandra Evans, Wendy Ribble, Erin Schexnaydre, Grover L. Waldrop
      Acetyl-CoA carboxylase (ACC) in bacteria is composed of three components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. ACC catalyzes the first committed step in fatty acid synthesis: the carboxylation of acetyl-CoA to form malonyl-CoA via a two-step reaction. In the first half-reaction, biotin carboxylase catalyzes the ATP-dependent carboxylation of the vitamin biotin covalently linked to biotin carboxyl carrier protein. In the second half-reaction, the carboxyl group is transferred from biotin to acetyl-CoA by the enzyme carboxyltransferase, to form malonyl-CoA. In most Gram-negative and Gram-positive bacteria, the three components of ACC form a complex that requires communication for catalysis, and is subject to feedback inhibition by acylated-acyl carrier proteins. This study investigated the mechanism of inhibition of palmitoyl-acyl carrier protein (PACP) on ACC. Unexpectedly, ACC was found to exhibit a significant hysteresis, meaning ACC was subject to inhibition by PACP in a time dependent manner. Pull-down assays demonstrated PACP does not prevent formation of the multiprotein complex, while steady-state kinetic analyses showed PACP inhibited ACC activity allosterically. Structure-activity analyses revealed that the pantothenic acid moiety of PACP is responsible for the inhibition of ACC. This study provides the first evidence of the hysteretic nature of ACC.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 636 (2017)
  • Silencing of Glut1 induces chemoresistance via modulation of
           Akt/GSK-3β/β-catenin/survivin signaling pathway in breast cancer cells
    • Authors: Sunhwa Oh; Hyungjoo Kim; KeeSoo Nam; Incheol Shin
      Pages: 110 - 122
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Sunhwa Oh, Hyungjoo Kim, KeeSoo Nam, Incheol Shin
      Cancer cells require increased aerobic glycolysis to support rapid cell proliferation. For their increased energy demands, cancer cells express glucose transporter (Glut) proteins at a high level. Glut1 is associated with basal-like breast cancer and is considered a potential therapeutic target. To investigate the possibility of Glut1 as a therapeutic target in breast cancer cells, we downregulated Glut1 in triple-negative breast cancer (TNBC) cell lines using a short hairpin system. We determined whether Glut1 silencing might enhance anti-proliferative effect of chemotherapeutic agents. Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3β (Ser9)/β-catenin/survivin. These results indicated that the potential of Glut1 as a therapeutic target should be carefully reevaluated.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 636 (2017)
  • Insights on the conformational dynamics of human frataxin through
           modifications of loop-1
    • Authors: Martín E. Noguera; Martín Aran; Clara Smal; Diego S. Vazquez; María Georgina Herrera; Ernesto A. Roman; Nadine Alaimo; Mariana Gallo; Javier Santos
      Pages: 123 - 137
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): Martín E. Noguera, Martín Aran, Clara Smal, Diego S. Vazquez, María Georgina Herrera, Ernesto A. Roman, Nadine Alaimo, Mariana Gallo, Javier Santos
      Human frataxin (FXN) is a highly conserved mitochondrial protein involved in iron homeostasis and activation of the iron-sulfur cluster assembly. FXN deficiency causes the neurodegenerative disease Friedreich's Ataxia. Here, we investigated the effect of alterations in loop-1, a stretch presumably essential for FXN function, on the conformational stability and dynamics of the native state. We generated four loop-1 variants, carrying substitutions, insertions and deletions. All of them were stable and well-folded proteins. Fast local motions (ps-ns) and slower long-range conformational dynamics (μs-ms) were altered in some mutants as judged by NMR. Particularly, loop-1 modifications impact on the dynamics of a distant region that includes residues from the β-sheet, helix α1 and the C-terminal. Remarkably, all the mutants retain the ability to activate cysteine desulfurase, even when two of them exhibit a strong decrease in iron binding, revealing a differential sensitivity of these functional features to loop-1 perturbation. Consequently, we found that even for a small and relatively rigid protein, engineering a loop segment enables to alter conformational dynamics through a long-range effect, preserving the native-state structure and important aspects of function.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 636 (2017)
  • GADD45 family proteins suppress JNK signaling by targeting MKK7
    • Authors: Takumi Ueda; Yuri Kohama; Ayana Kuge; Eriko Kido; Hiroshi Sakurai
      Pages: 1 - 7
      Abstract: Publication date: Available online 14 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Takumi Ueda, Yuri Kohama, Ayana Kuge, Eriko Kido, Hiroshi Sakurai
      Growth arrest and DNA damage-inducible 45 (GADD45) family genes encode related proteins, including GADD45α, GADD45β, and GADD45γ. In HeLa cells, expression of GADD45 members is differentially regulated under a variety of environmental conditions, but thermal and genotoxic stresses induce the expression of all genes. The heat shock response of GADD45β is mediated by the heat shock transcription factor 1 (HSF1), and GADD45β is necessary for heat stress survival. Heat and genotoxic stress-induced activation of c-Jun N-terminal kinase (JNK) is suppressed by the expression of GADD45 proteins. GADD45 proteins bind the JNK kinase mitogen-activated protein kinase kinase 7 (MKK7) and inhibit its activity, even under normal physiological conditions. Our findings indicate that GADD45 essentially suppresses the MKK7-JNK pathway and suggest that differentially expressed GADD45 family members fine-tune stress-inducible JNK activity.

      PubDate: 2017-10-14T08:31:24Z
      DOI: 10.1016/
      Issue No: Vol. 635 (2017)
  • Genotoxic effect and antigen binding characteristics of SLE
           auto-antibodies to peroxynitrite-modified human DNA
    • Authors: Md Asad Khan; Khursheed Alam; Syed Hassan Mehdi; M. Moshahid A. Rizvi
      Pages: 8 - 16
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Md Asad Khan, Khursheed Alam, Syed Hassan Mehdi, M. Moshahid A. Rizvi
      Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE.

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/
      Issue No: Vol. 635 (2017)
  • Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic phytol
    • Authors: Avery L. McIntosh; Stephen M. Storey; Huan Huang; Ann B. Kier; Friedhelm Schroeder
      Pages: 17 - 26
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Avery L. McIntosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm Schroeder
      While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% phytol. GC/MS showed that hepatic: i) phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary phytol in WT females, but only slightly in WT males; iii) accumulation of phytol and BCFA was further increased by DKO in phytol-fed females, but much more markedly in males. Livers of phytol-fed WT female mice as well as phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver phytol accumulation was not due to increased SCP-2 binding/transport of phytol since SCP-2 bound phytanic acid, but not its precursor phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary phytol and BCFA.
      Graphical abstract image

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/
      Issue No: Vol. 635 (2017)
  • Dielectric properties of plasma membrane: A signature for dyslipidemia in
           diabetes mellitus
    • Authors: Kakali Ghoshal; Subhadip Chakraborty; Chirantan Das; Sanatan Chattopadhyay; Subhankar Chowdhury; Maitree Bhattacharyya
      Pages: 27 - 36
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Kakali Ghoshal, Subhadip Chakraborty, Chirantan Das, Sanatan Chattopadhyay, Subhankar Chowdhury, Maitree Bhattacharyya
      Dielectric properties of a living biological membrane play crucial role indicating the status of the cell in pathogenic or healthy condition. A distinct variation in membrane capacitance and impedance was observed for peripheral blood mononuclear cell (PBMC) suspensions for diabetic and diabetic-dyslipidemic subjects compared to healthy control. Low frequency region were explicitly considered in electrical analysis to address complex membrane dielectric factors that alter the system capacitance of a PBMC suspension. Such variation was marked in size, morphology and membrane function of PBMCs for control and diseased cases. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) studies reveal significant alteration in surface morphology of PBMCs in diseased condition. Side scatter of flow cytometry reveals complexity of PBMCs in diseased condition. Changes in size between groups were not found by SEM and forward scatter. Functional alteration in PBMCs was manifested by significant changes in cell membrane properties like Na+, K+ ATPase and Ca2+, Mg2+ ATPase activity, reduced plasma membrane fluidity and changes in intracellular Ca2+ content, which bear significant correlation in diabetic and diabetic dyslipidemic subjects. Therefore, dielectric parameters of PBMCs in diabetic-dyslipidemic challenges may led to interesting correlation opening the possibility of identifying crucial signature biomarkers.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
      Issue No: Vol. 635 (2017)
  • Raman spectroscopy reveals the lipid phase transition in preimplantation
           mouse embryos during freezing
    • Authors: K.A. Okotrub; S.Y. Amstislavsky; N.V. Surovtsev
      Pages: 37 - 43
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): K.A. Okotrub, S.Y. Amstislavsky, N.V. Surovtsev
      Although lipid phase transition is believed to be among the major damaging factors in oocytes and preimplantation embryos cryopreservation, lack of the appropriate experimental methods limits investigation of this phenomenon. Herein, we demonstrate the capabilities of Raman spectroscopy to detect the lipid phase transition within the freezing preimplantation mouse embryos. We exploit the sensibility of antisymmetric CH2 Raman peak to the phase state of lipids. It is shown that during the freezing of the mouse embryos the lipid phase transition occurs at the temperatures between −7 and 0 °C. Similar temperature dependences of CH2 mode intensities are found for lipids in the preimplantation embryos and a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, implying the similarity in the occupation rules of conformational states. Raman spectroscopy is considered as a method of choice to study the lipid phase transition during preimplantation mammalian embryos freezing and cryopreservation.
      Graphical abstract image

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
      Issue No: Vol. 635 (2017)
  • Prothymosin α interacts with SET, ANP32A and ANP32B and other cytoplasmic
           and mitochondrial proteins in proliferating cells
    • Authors: Pablo Barbeito; Concepción S. Sarandeses; Cristina Díaz-Jullien; Juan Muras; Guillermo Covelo; David Moreira; Carmen Freire-Cobo; Manuel Freire
      Pages: 74 - 86
      Abstract: Publication date: 1 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 635
      Author(s): Pablo Barbeito, Concepción S. Sarandeses, Cristina Díaz-Jullien, Juan Muras, Guillermo Covelo, David Moreira, Carmen Freire-Cobo, Manuel Freire
      Prothymosin α (ProTα) is an acidic protein with a nuclear role related to the chromatin activity through its interaction with histones in mammalian cells. ProTα acts as an anti-apoptotic factor involved in the control of the apoptosome activity in the cytoplasm, however the mechanisms underlying this function are still known. ProTα shares similar biological functions with acidic nuclear-cytoplasmic shuttling proteins included in SET and ANP32 family members. Using affinity chromatography, co-immunoprecipitation and chemical cross-linking, we demonstrate that ProTα interacts with SET, ANP32A and ANP32B proteins. The study by mass spectrometry of the complexes stabilized by chemical cross-linking showed that associations of ProTα consist of six highly acidic ProTα-complexes, which corresponds to differentiated interactions of ProTα either with SET or ANP32 proteins. The presence in the ProTα-complexes of cytoplasmic proteins involved in membrane remodeling and proteins implicated in the mitochondrial permeability, seems to indicate that they could be related to a cytoplasmic-mitochondrial activity. According to the cellular function of the characterized targets of ProTα, and the evolution in the composition of the diverse ProTα-complexes when proliferation activity was reduced or apoptosis induced, leads to hypothesized that ProTα interactions might be related to the proliferation activity and control of the cell survival.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
      Issue No: Vol. 635 (2017)
  • Automatic regulation of NF-κB by pHSP70/IκBαm to prevent
           acute lung injury in mice
    • Authors: Hai-Ying Dong; Yan Cui; Bo Zhang; Ying Luo; Yan-Xia Wang; Ming-Qing Dong; Man-Ling Liu; Peng-Tao Zhao; Wen Niu; Zhi-Chao Li
      Pages: 47 - 56
      Abstract: Publication date: 15 November 2017
      Source:Archives of Biochemistry and Biophysics, Volume 634
      Author(s): Hai-Ying Dong, Yan Cui, Bo Zhang, Ying Luo, Yan-Xia Wang, Ming-Qing Dong, Man-Ling Liu, Peng-Tao Zhao, Wen Niu, Zhi-Chao Li
      Controlling target gene expression is a vital step in the procedure of gene therapy upon acute lung injury (ALI). Excessive activation of nuclear factor-kappa B (NF-κB) has been the key point of the inflammation overwhelming process in onset of ALI. We designed and tested a variety of plasmid named pHSP70/IκBαm which conditionally carries a mutant inhibitor of kappa B (IκB) transgene to regulate the activity of NF-κB signaling pathway in its response to an inflammatory stimulus that causes acute lung injury. Results recorded along our experiments showed that pHSP70/IκBαm was able to control mutant IκB expression in RAW264.7 cells with reference to the level of inflammatory response induced by LPS, thereby inhibiting NF-κB activation and downstream inflammatory cytokine expression. Vivo experiments revealed that construction naming pHSP70/IκBαm reduced LPS-induced lung injury and the secretion of inflammatory factors from lungs, hearts, and livers of sample mice in a LPS dose-dependent manner. In conclusion, the promoter heat shocking protein 70(HSP70) regulatory sequence of the construction was shown to drive mutant IκB expression so that its levels were positively associated with the dose of LPS used to induce acute lung injury. NF-κB activation and the downstream expression of inflammatory factors were therefore down-regulated in along an efficient path and ameliorating the damage as a consequence of LPS-induced acute lung injury.

      PubDate: 2017-10-14T08:31:24Z
      DOI: 10.1016/
      Issue No: Vol. 634 (2017)
  • Mild palmitate treatment increases mitochondrial mass but does not affect
           EA.hy926 endothelial cells viability
    • Authors: Dorota Dymkowska; Maria Kawalec; Tomasz Wyszomirski; Krzysztof Zabłocki
      Pages: 88 - 95
      Abstract: Publication date: 15 November 2017
      Source:Archives of Biochemistry and Biophysics, Volume 634
      Author(s): Dorota Dymkowska, Maria Kawalec, Tomasz Wyszomirski, Krzysztof Zabłocki
      A dyslipidaemia-related increase of the concentration of long-chain fatty acids in the plasma is an important pathological factor substantially increasing risk of serious consequences in vascular endothelium. Inflammatory response, atherosclerosis and insulin resistance seem the most severe. Palmitate at excessive concentrations has been shown to have a harmful effect on endothelial cells impairing NO generation, stimulating reactive oxygen species (ROS) formation and affecting their viability. On the other hand we found that palmitate applied for 48 h at 100 μM concentration which is sufficient to induce inflammatory response, increase ROS generation and reduce insulin sensitivity of EA.hy926 cells, unexpectedly also stimulates NO synthesis and increases mitochondrial mass, suggesting a pro-survival rather than anti-survival effect. This finding unveils a potential protective mechanism allowing cells to maintain their energy homeostasis under conditions of a moderate deregulation of lipid metabolism.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/
      Issue No: Vol. 634 (2017)
  • The inhibitory effects of biomimetically designed peptides on
           α-synuclein aggregation
    • Authors: Niloofar Rezaeian; Niloofar Shirvanizadeh; Soheila Mohammadi; Maryam Nikkhah; Seyed Shahriar Arab
      Pages: 96 - 106
      Abstract: Publication date: 15 November 2017
      Source:Archives of Biochemistry and Biophysics, Volume 634
      Author(s): Niloofar Rezaeian, Niloofar Shirvanizadeh, Soheila Mohammadi, Maryam Nikkhah, Seyed Shahriar Arab
      Parkinson's disease is characterized by accumulation of inclusion bodies in dopaminergic neurons, where insoluble and fibrillar α-synuclein makes up the major component of these inclusion bodies. So far, several strategies have been applied in order to suppress α-synuclein aggregation and toxicity in Parkinson's disease. In the present study, a new database has been established by segmentation of all the proteins deposited in protein Data Bank. The database data base was searched for the sequences which adopt β structure and are identical or very similar to the regions of α-synuclein which are involved in aggregation. The adjacent β strands of the found sequences were chosen as the peptide inhibitors of α-synuclein aggregation. Two of the predicted peptides, namely KISVRV and GQTYVLPG, were experimentally proved to be efficient in suppressing aggregation of α-synuclein in vitro. Moreover, KISVRV exhibited the ability to disrupt oligomers of α-syn which are assumed to be the pathogenic species in Parkinson's disease.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
      Issue No: Vol. 634 (2017)
  • Topoisomerase IIβ and its role in different biological contexts
    • Authors: V. Satish Bollimpelli; Pankaj S. Dholaniya; Anand K. Kondapi
      Pages: 78 - 84
      Abstract: Publication date: 1 November 2017
      Source:Archives of Biochemistry and Biophysics, Volume 633
      Author(s): V. Satish Bollimpelli, Pankaj S. Dholaniya, Anand K. Kondapi
      Topoisomerase IIβ is a type II DNA topoisomerase that was reported to be expressed in all mammalian cells but abundantly expressed in cells that have undergone terminal differentiation to attain a post mitotic state. Enzymatically it catalyzes ATP-dependent topological changes of double stranded DNA, while as a protein it was reported to be associated with several factors in promoting cell growth, migration, DNA repair and transcription regulation. The cellular roles of topoisomerase IIβ are very less understood compared to its counterpart topoisomerase IIα. This review discusses origin of Topoisomerase II beta, its structure, activities reported in vitro and in vivo along with implications in cellular processes namely transcription, DNA repair, neuronal development, aging, HIV-infection and cancer.

      PubDate: 2017-09-15T00:12:36Z
      DOI: 10.1016/
      Issue No: Vol. 633 (2017)
  • Functional significance of C-terminal mobile domain of cardiac troponin I
    • Authors: Nazanin Bohlooli Ghashghaee; Peter O. Awinda; Bertrand C.W. Tanner; Wen-Ji Dong
      Pages: 256a - 257a
      Abstract: Publication date: Available online 27 September 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Nazanin Bohlooli Ghashghaee, Bertrand C.W. Tanner, Wen-Ji Dong
      Ca2+-regulation of cardiac contractility is mediated through the troponin complex, which comprises three subunits: cTnC, cTnI, and cTnT. As intracellular [Ca2+] increases, cTnI reduces its binding interactions with actin to primarily interact with cTnC, thereby enabling contraction. A portion of this regulatory switching involves the mobile domain of cTnI (cTnI-MD), the role of which in muscle contractility is still elusive. To study the functional significance of cTnI-MD, we engineered two cTnI constructs in which the MD was truncated to various extents: cTnI(1–167) and cTnI(1–193). These truncations were exchanged for endogenous cTnI in skinned rat papillary muscle fibers, and their influence on Ca2+-activated contraction and cross-bridge cycling kinetics was assessed at short (1.9 μm) and long (2.2 μm) sarcomere lengths (SLs). Our results show that the cTnI(1–167) truncation diminished the SL-induced increase in Ca2+-sensitivity of contraction, but not the SL-dependent increase in maximal tension, suggesting an uncoupling between the thin and thick filament contributions to length dependent activation. Compared to cTnI(WT), both truncations displayed greater Ca2+-sensitivity and faster cross-bridge attachment rates at both SLs. Furthermore, cTnI(1–167) slowed MgADP release rate and enhanced cross-bridge binding. Our findings imply that cTnI-MD truncations affect the blocked-to closed-state transition(s) and destabilize the closed-state position of tropomyosin.

      PubDate: 2017-10-04T03:45:58Z
      DOI: 10.1016/j.bpj.2016.11.1399
      Issue No: Vol. 112, No. 3 (2017)
  • Naringin prevents the inhibition of intestinal Ca2+ absorption induced by
           a fructose rich diet
    • Authors: V.A. Rodríguez; M.A. Rivoira; S. Guizzardi; N.G. Tolosa de Talamoni
      Pages: 299 - 300
      Abstract: Publication date: 15 December 2017
      Source:Archives of Biochemistry and Biophysics, Volume 636
      Author(s): V. Rodríguez, M. Rivoira, S. Guizzardi, N. Tolosa de Talamoni
      This study tries to elucidate the mechanisms by which fructose rich diets (FRD) inhibit the rat intestinal Ca2+ absorption, and determine if any or all underlying alterations are prevented by naringin (NAR). Male rats were divided into: 1) controls, 2) treated with FRD, 3) treated with FRD and NAR. The intestinal Ca2+ absorption and proteins of the transcellular and paracellular Ca2+ pathways were measured. Oxidative/nitrosative stress and inflammation parameters were evaluated. FRD rats showed inhibition of the intestinal Ca2+ absorption and decrease in the protein expression of molecules of both Ca2+ pathways, which were blocked by NAR. FRD rats showed an increase in the superoxide anion, a decrease in the glutathione and in the enzymatic activities of the antioxidant system, as well as an increase in the NO content and in the nitrotyrosine content of proteins. They also exhibited an increase in both IL-6 and nuclear NF-κB. All these changes were prevented by NAR. In conclusion, FRD inhibit both pathways of the intestinal Ca2+ absorption due to the oxidative/nitrosative stress and inflammation. Since NAR prevents the oxidative/nitrosative stress and inflammation, it might be a drug to avoid alteration in the intestinal Ca2+ absorption caused by FRD.
      Graphical abstract image

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/j.bone.2017.03.012
      Issue No: Vol. 105 (2017)
  • Characterizing interaction forces between actin and proteins of the
           tropomodulin family reveals the presence of the N-terminal actin-binding
           site in leiomodin
    • Authors: Baran Arslan; Mert Colpan; Kevin T. Gray; Nehal I. Abu-Lail; Alla S. Kostyukova
      Abstract: Publication date: Available online 6 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Baran Arslan, Mert Colpan, Kevin T. Gray, Nehal I. Abu-Lail, Alla S. Kostyukova
      Tropomodulin family of proteins includes several isoforms of tropomodulins (Tmod) and leiomodins (Lmod). These proteins can sequester actin monomers or nucleate actin polymerization. Although it is known that their actin-binding properties are isoform-dependent, knowledge on how they vary in strengths of interactions with G-actin is missing. While it is confirmed in many studies that Tmods have two actin-binding sites, information on number and location of actin-binding sites in Lmod2 is controversial. We used atomic force microscopy to study interactions between G-actin and proteins of the tropomodulin family. Unbinding forces between G-actin and Tmod1, Tmod2, Tmod3, or Lmod2 were quantified. Our results indicated that Tmod1 and Tmod3 had unimodal force distributions, Tmod2 had a bimodal distribution and Lmod2 had a trimodal distribution. The number of force distributions correlate with the proteins abilities to sequester actin or nucleate actin polymerization. We assigned specific unbinding forces to the individual actin-binding sites of Tmod2 and Lmod2 using mutations that destroy actin-binding sites of Tmod2 and truncated Lmod2. Our results confirm the existence of the N-terminal actin-binding site in Lmod2. Altogether, our data demonstrate how the differences between the number and the strength of actin-binding sites of Tmod or Lmod translate to their functional abilities.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
  • Understanding the molecular basis of the high oxygen affinity variant
           human hemoglobin Coimbra
    • Authors: S.E. Jorge; M. Bringas; A.A. Petruk; M. Arrar; M.A. Marti; M.S. Skaf; F.F. Costa; L. Capece; M.F. Sonati; D. Estrin
      Abstract: Publication date: Available online 1 December 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): S.E. Jorge, M. Bringas, A.A. Petruk, M. Arrar, M.A. Marti, M.S. Skaf, F.F. Costa, L. Capece, M.F. Sonati, D. Estrin
      Human hemoglobin (Hb) Coimbra (βAsp99Glu) is one of the seven βAsp99 Hb variants described to date. All βAsp99 substitutions result in increased affinity for O2 and decreased heme-heme cooperativity and their carriers are clinically characterized by erythrocytocis, caused by tissue hypoxia. Since βAsp99 plays an important role in the allosteric α1β2 interface and the mutation in Hb Coimbra only represents the insertion of a CH2 group in this interface, the present study of Hb Coimbra is important for a better understanding of the global impact of small modifications in this allosteric interface. We carried out functional, kinetic and dynamic characterization of this hemoglobin, focusing on the interpretation of these results in the context of a growth of the position 99 side chain length in the α1β2 interface. Oxygen affinity was evaluated by measuring p50 values in distinct pHs (Bohr effect), and the heme-heme cooperativity was analyzed by determining the Hill coefficient (n), in addition to the effect of the allosteric effectors inositol hexaphosphate (IHP) and 2,3-bisphosphoglyceric acid (2,3-BPG). Computer simulations revealed a stabilization of the R state in the Coimbra variant with respect to the wild type, and consistently, the T-to-R quaternary transition was observed on the nanosecond time scale of classical molecular dynamics simulations.

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
  • Role of hydroxyl groups in the B-ring of flavonoids in stabilization of
           the Hoogsteen paired third strand of Poly(U).Poly(A)*Poly(U) triplex
    • Authors: Ankur Bikash Pradhan; Sutanwi Bhuiya; Lucy Haque; Suman Das
      Abstract: Publication date: Available online 21 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ankur Bikash Pradhan, Sutanwi Bhuiya, Lucy Haque, Suman Das
      We have reported the interaction of two flavonoids namely quercetin (Q) and morin (M) with double stranded poly(A).poly(U) (herein after A.U) and triple stranded poly(U).poly(A)*poly(U) (herein after U.A*U, dot represents the Watson–Crick and asterisk represents Hoogsteen base pairing respectively) in this article. It has been observed that relative positions of hydroxyl groups on the B-ring of the flavonoids affect the stabilization of RNA. The double strand as well as the triple strand of RNA-polymers become more stabilized in presence of Q, however both the duplex and triplex remain unaffected in presence of M. The presence of catechol moiety on the B-ring of Q is supposed to be responsible for the stabilization. Moreover, after exploiting a series of biophysical experiments, it has been found that, triple helical RNA becomes more stabilized over its parent duplex in presence of Q. Fluorescence quenching, viscosity measurement and helix melting results establish the fact that Q binds with both forms of RNA through the mode of intercalation while M does not bind at all to either forms of RNA.
      Graphical abstract image

      PubDate: 2017-12-07T23:51:11Z
      DOI: 10.1016/
  • Kinetics and thermodynamics of the thermal inactivation and chaperone
           assisted folding of zebrafish dihydrofolate reductase
    • Authors: Charu Thapliyal; Neha Jain; Naira Rashid; Pratima Chaudhuri
      Abstract: Publication date: Available online 11 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Charu Thapliyal, Neha Jain, Naira Rashid, Pratima Chaudhuri
      The maintenance of thermal stability is a major issue in protein engineering as many proteins tend to form inactive aggregates at higher temperatures. Zebrafish DHFR, an essential protein for the survival of cells, shows irreversible thermal unfolding transition. The protein exhibits complete unfolding and loss of activity at 50 °C as monitored by UV-Visible, fluorescence and far UV-CD spectroscopy. The heat induced inactivation of zDHFR follows first–order kinetics and Arrhenius law. The variation in the value of inactivation rate constant, k with increasing temperatures depicts faster inactivation at elevated temperatures. We have attempted to study the chaperoning ability of a shorter variant of GroEL (minichaperone) and compared it with that of conventional GroEL-GroES chaperone system. Both the chaperone system prevented the aggregation and assisted in refolding of zDHFR. The rate of thermal inactivation was significantly retarded in the presence of chaperones which indicate that it enhances the thermal stability of the enzyme. As minichaperone is less complex, and do not require high energy co-factors like ATP, for its function as compared to conventional GroEL-GroES system, it can act as a very good in vitro as well as in vivo chaperone model for monitoring assisted protein folding phenomenon.

      PubDate: 2017-11-15T16:22:32Z
      DOI: 10.1016/
  • SNHG16/miR-216-5p/ZEB1 signal pathway contributes to the tumorigenesis of
           cervical cancer cells
    • Authors: Hong Zhu; Yan Zeng; Chen-chen Zhou; Weiping Ye
      Abstract: Publication date: Available online 7 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hong Zhu, Yan Zeng, Chen-chen Zhou, Weiping Ye
      Long non-coding RNAs (lncRNAs) have been confirmed as crucial regulators in tumorgenesis. Small nucleolar RNA host gene 16 (SNHG16) has been recently uncovered to be a potential oncogene in several types of cancers. However, its expression level and potential role in cervical cancer remain uncertain. In our research, we assessed the expression level of SNHG16 in clinical cervical cancer tissues and cells. We made use of functional assays to determine the biological effects of SNHG16 on cell proliferation and migration of cervical cancer. By employing the bioinformatics analysis tools, we revealed that miR-216-5p could interact with SNHG16 and there existed a negative correlation between the expression levels of miR-216-5p and SNHG16 in cervical cancer specimens. Furthermore, RIP assay, RNA pulldown system and dual luciferase reporter assays confirmed that SNHG16 directly targeted miR-216-5p by harboring the binding sites of microRNA in the SNHG16 sequence. Additionally, bioinformatics analysis provided an evidence that ZEB1 was a potential target of miR-216-5p. Collectively, it was suggested that SNHG16 could serve as an oncogene that promoted tumor progression by acting as an endogenous ‘sponge’ to regulate miR-216A-5p/ZEB1.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/
  • JNK signaling pathway regulates sorbitol-induced Tau proteolysis and
           apoptosis in SH-SY5Y cells by targeting caspase-3
    • Authors: Marta Olivera Santa-Catalina; Montaña Caballero Bermejo; Ricardo Argent; Juan C. Alonso; Francisco Centeno; María J. Lorenzo
      Abstract: Publication date: Available online 7 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Marta Olivera Santa-Catalina, Montaña Caballero Bermejo, Ricardo Argent, Juan C. Alonso, Francisco Centeno, María J. Lorenzo
      Growing evidence suggests that Diabetes Mellitus increases the risk of developing Alzheimer's disease. It is well known that hyperglycemia, a key feature of Diabetes Mellitus, may induce plasma osmolarity disturbances. Both hyperglycemia and hyperosmolarity promote the altered post-translational regulation of microtubule-associated protein Tau. Interestingly, abnormal hyperphosphorylation and cleavage of Tau have been proven to lead to the genesis of filamentous structures referred to as neurofibrillary tangles, the main pathological hallmark of Alzheimer's disease. We have previously described that hyperosmotic stress induced by sorbitol promotes Tau proteolysis and apoptosis in SH-SY5Y cells via caspase-3 activation. In order to gain insights into the regulatory mechanisms of such processes, in this work we explored the intracellular signaling pathways that regulate these events. We found that sorbitol treatment significantly enhanced the activation of conventional families of MAPK in SH-SY5Y cells. Tau proteolysis was completely prevented by JNK inhibition but not affected by either ERK1/2 or p38 MAPK blockade. Moreover, inhibition of JNK, but not ERK1/2 or p38 MAPK, efficiently prevented sorbitol-induced apoptosis and caspase-3 activation. In summary, we provide evidence that JNK signaling pathway is an upstream regulator of hyperosmotic stress-induced Tau cleavage and apoptosis in SH-SY5Y through the control of caspase-3 activation.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/
  • Physiological serum copper concentrations found in malignancies cause
           unfolding induced aggregation of human serum albumin in vitro
    • Authors: Asim Rizvi; Mohd Furkan; Imrana Naseem
      Abstract: Publication date: Available online 6 November 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Asim Rizvi, Mohd Furkan, Imrana Naseem
      Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed.

      PubDate: 2017-11-08T15:55:15Z
      DOI: 10.1016/
  • Thermodynamics of cooperative binding of FAD to human NQO1: Implications
           to understanding cofactor-dependent function and stability of the
    • Authors: Rafael Clavería-Gimeno; Adrian Velazquez-Campoy; Angel Luis Pey
      Abstract: Publication date: Available online 31 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rafael Clavería-Gimeno, Adrian Velazquez-Campoy, Angel Luis Pey
      The stability of human flavoproteins strongly depends on flavin levels, although the structural and energetic basis of this relationship is poorly understood. Here, we report an in-depth analysis on the thermodynamics of FAD binding to one of the most representative examples of such relationship, NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 is a dimeric enzyme that tightly binds FAD, which triggers large structural changes upon binding. A common cancer-associated polymorphism (P187S) severely compromises FAD binding. We show that FAD binding is described well by a thermodynamic model explicitly incorporating binding cooperativity when applied to different sets of calorimetric analyses and NQO1 variants, thus providing insight on the effects in vitro and in cells of cancer-associated P187S, its suppressor mutation H80R and the role of NQO1 C-terminal domain to modulate binding cooperativity and energetics. Furthermore, we show that FAD binding to NQO1 is very sensitive to physiologically relevant environmental conditions, such as the presence of phosphate buffer and salts. Overall, our results contribute to understanding at the molecular level the link between NQO1 stability and fluctuations of FAD levels intracellularly, and supports the notion that FAD binding energetics and cooperativity are fundamentally linked with the dynamic nature of apo-NQO1 conformational ensemble.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • Isomer distribution of hydroxyoctadecadienoates (HODE) and
           hydroxyeicosatetraenoates (HETE) produced in the plasma oxidation mediated
           by peroxyl radical, peroxynitrite, hypochlorite, 15-lipoxygenase, and
           singlet oxygen
    • Authors: Aya Umeno; Mayuko Morita; Yasukazu Yoshida; Yuji Naito; Etsuo Niki
      Abstract: Publication date: Available online 31 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Aya Umeno, Mayuko Morita, Yasukazu Yoshida, Yuji Naito, Etsuo Niki
      Free and ester forms of unsaturated fatty acids and cholesterol are oxidized in vivo by multiple oxidants to give diverse products. Some lipid oxidation is mediated by enzymes to selectively give specific products, while others proceed randomly to produce mixtures of many kinds of regioisomers and stereoisomers. The efficacy of antioxidants against lipid oxidation depends on the nature of the oxidants and therefore the identification of oxidant is important for understanding the roles and effects of lipid oxidation and antioxidants in vivo. In the present study, the isomer distribution of hydro(pero)xyoctadecadienoates (H(p)ODEs) and hydro(pero)xyeicosatetraenoates (H(p)ETEs), the most abundant lipid oxidation products found in human plasma, produced in the oxidation of plasma by peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen were examined. It was shown that 9- and 13-(E,E)-HODEs, 13(S)-(Z,E)-HODE, and 10- and 12-(Z,E)-HODEs were specific lipid oxidation products by free radical, 15-lipoxygenase, and singlet oxygen, respectively. The isomer distribution of HODEs produced by peroxynitrite was similar to that by peroxyl radical, suggesting that the peroxynitrite mediated lipid oxidation proceeds by free radical mechanisms. The production of HODEs and HETEs by hypochlorite was very small. HODEs may be a better biomarker than HETEs since linoleates are oxidized by simpler mechanisms than arachidonates and all the HODEs isomers can be quantified more easily. These products may be used as specific biomarkers for the identification of responsible oxidants and for the assessment of oxidant-specific lipid oxidation levels and effects of antioxidants in vivo.
      Graphical abstract image

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • CagL from Helicobacter pylori has ADP-ribosylation activity and exerts
           partial protective efficacy in mice
    • Authors: Eleonora Talluri; Laura Pancotto; Paolo Ruggiero; Maria Scarselli; Enrico Balducci
      Abstract: Publication date: Available online 31 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Eleonora Talluri, Laura Pancotto, Paolo Ruggiero, Maria Scarselli, Enrico Balducci
      Mono ADP-ribosyltransferases are a class of functionally conserved enzymes present in prokaryotic and eukaryotic organisms. In prokaryotes, mono ADP-ribose transfer enzymes often represent a family of exotoxins that display activity in a variety of bacteria responsible for causing disease in plants and animals. A bioinformatic approach has allowed us to identify that CagL gene from some Helicobacter pylori strains shares a sequence pattern with ADP-ribosylating toxins of the CT-group. In this manuscript we show that recombinant CagL from Shi470 is catalytically active showing ADP-ribosyltransferase, NAD-glycohydrolase, and auto-ADP-ribosylation activities. This is the first time that a catalytically active member of the ADP-ribosyltransferase family is identified in Helicobacter pylori. This observation may lead to the discovery of novel functions exerted by CagL in the pathogenesis of Helicobacter pylori. Indeed, we have shown that vaccination with CagL has protective efficacy in mice indicating that CagL may be considered as potential component of a Helicobacter pylori vaccine.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • Sexual dimorphism in oxidant-induced adaptive homeostasis in multiple
           wild-type D. melanogaster strains
    • Authors: Laura C.D. Pomatto; Sarah Wong; John Tower; Kelvin J.A. Davies
      Abstract: Publication date: Available online 31 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Laura C.D. Pomatto, Sarah Wong, John Tower, Kelvin J.A. Davies
      Sexual dimorphism includes the physical and reproductive differences between the sexes, including differences that are conserved across species, ranging from the common fruit fly, Drosophila melanogaster, to humans. Sex-dependent variations in adaptive homeostasis, and adaptive stress responses may offer insight into the underlying mechanisms for male and female survival differences and into differences in chronic disease incidence and severity in humans. Earlier work showed sex-specific differences in adaptive responses to oxidative stressors in hybrid laboratory strains of D. melanogaster. The present study explored whether this phenomenon is also observed in wild-type D. melanogaster strains Oregon-R (Or-R) and Canton-S (Ca-S), as well as the common mutant reference strain w[1118], in order to better understand whether such findings are descriptive of D. melanogaster in general. Flies of each strain were pretreated with non-damaging, adaptive concentrations of hydrogen peroxide (H2O2) or of different redox cycling agents (paraquat, DMNQ, or menadione). Adaptive homeostasis, and changes in the expression of the proteasome and overall cellular proteasomal proteolytic capacity were assessed. Redox cycling agents exhibited a male-specific adaptive response, whereas H2O2 exposure provoked female-specific adaptation. These findings demonstrate that different oxidants can elicit sexually dimorphic adaptive homeostatic responses in multiple fly strains. These results (and those contained in a parallel study [1]) highlight the need to address sex as a biological variable in both fundamental science, clinical research, and toxicology.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • Ru/Fe bimetallic complexes: Synthesis, characterization, cytotoxicity and
           study of their interactions with DNA/HSA and human topoisomerase IB
    • Authors: Jessica E. Takarada; Adriana P.M. Guedes; Rodrigo S. Correa; Elisângela de P. Silveira-Lacerda; Silvia Castelli; Federico Iacovelli; Victor Marcelo Deflon; Alzir Azevedo Batista; Alessandro Desideri
      Abstract: Publication date: Available online 28 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jessica E. Takarada, Adriana P.M. Guedes, Rodrigo S. Correa, Elisângela de P. Silveira-Lacerda, Silvia Castelli, Federico Iacovelli, Victor Marcelo Deflon, Alzir Azevedo Batista, Alessandro Desideri
      Three ruthenium/iron-based compounds, 1: [Ru(MIm)(bipy)(dppf)]PF6 (MIm = 2-mercapto-1-methylimidazole anion), 2: [RuCl(Im)(bipy)(dppf)]PF6 (Im = imidazole), and 3: [Ru(tzdt)(bipy)(dppf)]PF6 (tzdt = 1,3-thiazolidine-2-thione anion) (dppf = 1,1′-bis(diphenylphosphine)ferrocene and bipy = 2,2′-bipyridine), were synthesized, and characterized by elemental analyses, conductivity, UV/Vis, IR, 1H, 13C and 31P{1H} NMR spectroscopies, and by electrochemical technique. The complex 3 was also characterized by single-crystal X-ray. The three ruthenium(II) complexes show cytotoxicity against DU-145 (prostate carcinoma cells) and A549 (lung carcinoma cells) tumor cells. The free ligands do not exhibit any cytotoxic activity, such as evident by the IC50 values higher than 200 μM. UV/Vis and viscosity experiments showed that the complexes interact weakly with the DNA molecule, via electrostatic forces. The interaction of the complexes 1–3 with the HSA is moderate, with Kb values in range of 105-107 M−1, presenting a static mechanism of interaction stabilized by hydrophobic. Complexes 2 and 3 showed high affinity for the FA7 HSA site as evidenced by fluorescence spectroscopy and molecular docking. Complexes 1–3 were tested as potential human Topoisomerase IB inhibitors by analysing the different steps of the enzyme catalytic cycle. The results indicate that all compounds efficiently inhibit the DNA relaxation and the cleavage reaction, in which the effect increases upon pre-incubation. Complexes 1 and 2 are also able to slow down the religation reaction.

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • Kinetic and structural characterization of a cis-3-Chloroacrylic acid
           dehalogenase homologue in Pseudomonas sp. UW4: A potential step between
           subgroups in the tautomerase superfamily
    • Authors: Jake A. LeVieux; Bert-Jan Baas; Tamer S. Kaoud; Rebecca Davidson; Patricia C. Babbitt; Yan Jessie Zhang; Christian P. Whitman
      Abstract: Publication date: Available online 27 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jake A. LeVieux, Bert-Jan Baas, Tamer S. Kaoud, Rebecca Davidson, Patricia C. Babbitt, Yan Jessie Zhang, Christian P. Whitman
      A Pseudomonas sp. UW4_01740 (designated Ps01740) protein of unknown function was identified as similar to 4-oxalocrotonate tautomerase (4-OT)-like and cis-3-chloroacrylic acid dehalogenase (cis-CaaD)-like subgroups of the tautomerase superfamily (TSF). Ps01740 lacks only Tyr-103 of the amino acids critical for cis-CaaD activity (Pro-1, His-28, Arg-70, Arg-73, Tyr-103, Glu-114). As Ps01740 may represent an important variant of these enzymes, its kinetic and structural properties have been determined. Ps01740 shows tautomerase activity with phenylenolpyruvate, but lacks native 4-OT activity and dehalogenase activity with the isomers of 3-chloroacrylic acid. Ps01740 shows mostly low-level hydratase activity at pH 7.0, converting 2-oxo-3-pentynoate to acetopyruvate, consistent with cis-CaaD-like behavior. At pH 9.0, this compound results primarily in covalent modification of Pro-1, which is consistent with 4-OT-like behavior. These observations could reflect a pK a for Pro-1 that is closer to that of cis-CaaD (∼9.2) than to 4-OT (∼6.4. A structure of the native enzyme, at 2.6 Å resolution, highlights differences at the active site from those of 4-OT and cis-CaaD that add to our understanding of how contemporary TSF reactions and mechanisms may have diverged from a common 4-OT-like ancestor.
      Graphical abstract image

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • Oxygen binding isotope effects of triazole-based HIV-1 reverse
           transcryptase inhibitors indicate the actual binding site
    • Authors: Agnieszka Krzemińska; Tomasz Frączek; P. Paneth
      Abstract: Publication date: Available online 27 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Agnieszka Krzemińska, Tomasz Frączek, P. Paneth
      Binding isotope effects (BIEs) associated with binding of four triazole-based ligands to HIV-1 reverse transcriptase have been calculated at the QM/MM MD level of theory. Two main binding sited; allosteric cavity and RNase H active site, as well as three other sites reported in the literature (the Knuckles, the NNRTI Adjacent, and Incoming Nucleotide Binding) have been considered. The interactions between inhibitors and these protein sites have been quantified by binding free energies obtained from free energy perturbation (FEP) calculations, supported by interaction energy analysis. It has been shown that binding in the allosteric cavity can be distinguished from binding to other sites based on BIEs as it is associated with normal 18O-BIEs of the carbonyl oxygen atom while binding to RNase H active site is characterized by inverse binding isotope effect (18O-BIE < 1). For other sites 18O-BIEs close to unity are predicted. This information points to oxygen binding isotope effects of carbonyl group as indicative of the actual binding site of studied inhibitors.
      Graphical abstract image

      PubDate: 2017-11-02T08:27:27Z
      DOI: 10.1016/
  • Insights into the role of methionine synthase in the universal 13C
           depletion in O- and N-methyl groups of natural products
    • Authors: Katarzyna M. Romek; Agnieszka Krzemińska; Gérald S. Remaud; Maxime Julien; Piotr Paneth; Richard J. Robins
      Abstract: Publication date: Available online 23 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Katarzyna M. Romek, Agnieszka Krzemińska, Gérald S. Remaud, Maxime Julien, Piotr Paneth, Richard J. Robins
      Many O-methyl and N-methyl groups in natural products are depleted in 13C relative to the rest of the molecule. These methyl groups are derived from the C-1 tetrahydrofolate pool via l-methionine, the principle donor of methyl units. Depletion could occur at a number of steps in the pathway. We have tested the hypothesis that methionine biosynthesis is implicated in this depletion by using a combined experimental and theoretical approach. By using isotope ratio monitoring 13C NMR spectrometry to measure the position-specific distribution of 13C within l-methionine of natural origin, it is shown that the S-methyl group is depleted in 13C by ∼20‰ relative to the other positions in the molecule. In parallel, we have conducted a basic theoretical analysis of the reaction pathway of methionine synthase to assess whether the enzyme cobalamine-independent l-methionine synthase (EC—that catalyzes the synthesis of l-methionine from 5-methyl-tetrahydrofolate and homocysteine— plays a role in causing this depletion. Calculation predicts a strong normal 13C kinetic isotope effect (1.087) associated with this enzyme. Hence, depletion in 13C in the S-methyl of l-methionine during biosynthesis can be identified as an important factor contributing to the general depletion seen in many O-methyl and N-methyl groups of natural products.
      Graphical abstract image

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/
  • Changes on serum and hepatic lipidome after a chronic cadmium exposure in
           Wistar rats
    • Authors: Victor Enrique Sarmiento-Ortega; Samuel Treviño; José Ángel Flores-Hernández; Patricia Aguilar-Alonso; Diana Moroni Gonzalez; Violeta Aburto Luna; Alfonso Diaz; Eduardo Brambila
      Abstract: Publication date: Available online 21 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Victor Enrique Sarmiento-Ortega, Samuel Treviño, José Ángel Flores-Hernández, Patricia Aguilar-Alonso, Diana Moroni Gonzalez, Violeta Aburto Luna, Alfonso Diaz, Eduardo Brambila

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/
  • Procyanidins from Cinnamomi Cortex promote proteasome-independent
           degradation of nuclear Nrf2 through phosphorylation of insulin-like growth
           factor-1 receptor in A549 cells
    • Authors: Tomokazu Ohnuma; Kazuya Sakamoto; Asumi Shinoda; Chiaki Takagi; Shoko Ohno; Takahito Nishiyama; Kenichiro Ogura; Akira Hiratsuka
      Abstract: Publication date: Available online 16 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Tomokazu Ohnuma, Kazuya Sakamoto, Asumi Shinoda, Chiaki Takagi, Shoko Ohno, Takahito Nishiyama, Kenichiro Ogura, Akira Hiratsuka
      Many lines of evidence demonstrate that transcription factor nuclear factor-E2-related factor 2 (Nrf2) plays essential roles in cancer cell proliferation and resistance to chemotherapy, thereby indicating that suppression of abnormal Nrf2 activation is needed for a new therapeutic approach. Our previous studies reported that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an ability to suppress cytoprotective enzymes and cell proliferation in human cancer cells with activated Nrf2. In the present study, we investigated the mechanism of CCE procyanidin-mediated antagonization of Nrf2. CCE procyanidin treatment rapidly reduced nuclear Nrf2 expression and phosphorylated insulin-like growth factor-1 receptor (IGF-1R) in A549 cells. Nrf2 protein expression in A549 cells with reduced IGF-1R expression and function was not affected by treatment with CCE procyanidins, which suggested that CCE procyanidins decreased Nrf2 through IGF-1R. Nrf2 suppression by CCE procyanidins was mitigated in the presence of protease inhibitors, not proteasome inhibitors. In addition, CCE procyanidin treatment led to enhancement of nuclear cysteine protease activity in A549 cells. Our findings suggest a novel mechanism by which CCE procyanidins can promote proteasome-independent degradation of nuclear Nrf2 through IGF-1R phosphorylation and cysteine protease activation.

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/
  • Increase of Bacillus badius Phenylalanine dehydrogenase specificity
           towards phenylalanine substrate by site-directed mutagenesis
    • Authors: Farzad Yousefi; Farangis Ataei; Seyed Shahriar Arab; Saman Hosseinkhani
      Abstract: Publication date: Available online 16 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Farzad Yousefi, Farangis Ataei, Seyed Shahriar Arab, Saman Hosseinkhani
      Phenylalanine dehydrogenase (PheDH) is a key enzyme in medical diagnostic for determining the amount of phenylalanine to detect phenylketonuria (PKU) disease. However, determination of phenylalanine can be usually disturbed in presence of tyrosine in blood samples. Position N145 of B.sphaericus PheDH, has been previously showed a crucial role in substrate binding, which corresponded by position V144 in B. badius PheDH. In this study, the PheDH of B. badius due to reasonable activity was cloned and subjected to site-directed mutagenesis at mentioned position, followed by kinetic and structural studies to find more exclusive mutants. The results showed that the V144L mutant considerably increases specificity toward phenylalanine and decreases toward L-tyrosine, while in V144N mutant, the specificity reduces toward phenylalanine and increases toward tyrosine. Moreover, concerning the mutated V144D, significantly reduced kcat and also decreased km value for phenylalanine relative to that of wild type. The Phe/Tyr specificity constant in V144L increased more than 4-fold compared to wild type, makes it to be a suitable candidate for more specific identification of PKU. Finally, docking and molecular dynamic simulation on wild type and mutants clarified the structural basis behind more specificity of V144L mutant for phenylalanine substrate.

      PubDate: 2017-10-26T07:19:33Z
      DOI: 10.1016/
  • Substitutions of S101 decrease proton and hydride transfers in the
           oxidation of betaine aldehyde by choline oxidase
    • Authors: Giovanni Gadda; Hongling Yuan
      Abstract: Publication date: Available online 10 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Giovanni Gadda, Hongling Yuan
      Choline oxidase oxidizes choline to glycine betaine, with two flavin-mediated reactions to convert the alcohol substrate to the carbon acid product. Proton abstraction from choline or hydrated betaine aldehyde in the wild-type enzyme occurs in the mixing time of the stopped-flow spectrophotometer, thereby precluding a mechanistic investigation. Mutagenesis of S101 rendered the proton transfer reaction amenable to study. Here, we have investigated the aldehyde oxidation reaction catalyzed by the mutant enzymes using steady-state and rapid kinetics with betaine aldehyde. Stopped-flow traces for the reductive half-reaction of the S101T/V/C variants were biphasic, corresponding to the reactions of proton abstraction and hydride transfer. In contrast, the S101A enzyme yielded monophasic traces like wild-type choline oxidase. The rate constants for proton transfer in the S101T/C/V variants decreased logarithmically with increasing hydrophobicity of residue 101, indicating a behavior different from that seen previously with choline for which no correlation was determined. The rate constants for hydride transfer also showed a logarithmic decrease with increasing hydrophobicity at position 101, which was similar to previous results with choline as a substrate for the enzyme. Thus, the hydrophilic character of S101 is necessary not only for efficient hydride transfer but also for the proton abstraction reaction.
      Graphical abstract image

      PubDate: 2017-10-11T08:24:40Z
  • STM2360 encodes a d-ornithine/d-lysine decarboxylase in Salmonella
           enterica serovar typhimurium
    • Authors: Robert Phillips; Pafe Poteh Katherine Miller Timothy Hoover
      Abstract: Publication date: Available online 9 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Robert S. Phillips, Pafe Poteh, Katherine A. Miller, Timothy R. Hoover
      STM2360 is a gene located in a small operon of undetermined function in Salmonella enterica serovar Typhimurium LT2. The amino acid sequence of STM2360 shows significant similarity (∼30% identity) to diaminopimelate decarboxylase (DapDC), a Fold III pyridoxal-5′-phosphate (PLP) dependent enzyme involved in l-lysine biosynthesis. We have found that the protein coded by STM2360 has a previously undocumented catalytic activity, d-ornithine/d-lysine decarboxylase (DOKDC). The reaction products, cadaverine and putrescine, respectively, were identified by NMR and mass spectrometry. The substrate specificity of DOKDC is d-Lysine > d-Ornithine. This is the first pyridoxal-5′-phosphate dependent decarboxylase identified to act on d-amino acids. STM2358, located in the same operon, has ornithine racemase activity. This suggests that the physiological substrate of the decarboxylase and the operon is ornithine. Homologs of STM2360 with high sequence identity (>80%) are found in other common enterobacteria, including species of Klebsiella, Citrobacter, Vibrio and Hafnia, as well as Clostridium in the Firmicutes, and Pseudomonas.
      Graphical abstract image

      PubDate: 2017-10-11T08:24:40Z
  • Characterization of the nuclear import pathway for BLM protein
    • Authors: Zhiqiang Duan; Jiafu Zhao Houqiang Haixu Xinqin Xiang Chen Jianming
      Abstract: Publication date: Available online 7 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Zhiqiang Duan, Jiafu Zhao, Houqiang Xu, Haixu Xu, Xinqin Ji, Xiang Chen, Jianming Xiong
      Numerous studies have shown that nuclear localization of BLM protein, a member of the RecQ helicases, mediated by nuclear localization signal (NLS) is critical for DNA recombination, replication and transcription, but the mechanism by which BLM protein is imported into the nucleus remains unknown. In this study, the nuclear import pathway for BLM was investigated. We found that nuclear import of BLM was inhibited by two dominant-negative mutants of importin β1 and NTF2/E42K, which lacks the ability to bind Ran and RanGDP, respectively, but was not inhibited by the Ran/Q69L, which is deficient in GTP hydrolysis. Further studies revealed that nuclear import of BLM was reconstituted using importin β1, RanGDP and NTF2 in digitonin-permeabilized HeLa cells. Moreover, BLM had direct binding to importin β1 through its NLS domain with the 14–16 HEAT repeats of importin β1. Furthermore, importin β1, Ran or NTF2 depletion by siRNA disrupted the accumulation of BLM protein in the nucleus. These results showed that BLM enters the nucleus via the importin β1, RanGDP and NTF2 dependent pathway, demonstrating for the first time the nuclear trafficking mechanism of a DNA helicase.
      Graphical abstract image

      PubDate: 2017-10-11T08:24:40Z
  • Selenoprotein MsrB1 deficiency exacerbates acetaminophen-induced
           hepatotoxicity via increased oxidative damage
    • Authors: Ki Young Kim; Geun-Hee Kwak; Mahendra Pratap Singh; Vadim N. Gladyshev; Hwa-Young Kim
      Abstract: Publication date: Available online 3 October 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ki Young Kim, Geun-Hee Kwak, Mahendra Pratap Singh, Vadim N. Gladyshev, Hwa-Young Kim
      Acetaminophen (APAP) overdose induces acute liver damage and failure via reactive oxygen species production and glutathione (GSH) depletion. Methionine sulfoxide reductase B1 (MsrB1) is an antioxidant selenoenzyme that specifically catalyzes the reduction of methionine R-sulfoxide residues. In this study, we used MsrB1 gene-knockout mice and primary hepatocytes to investigate the effect of MsrB1 on APAP-induced hepatotoxicity. Analyses of histological alterations and serum indicators of liver damage showed that MsrB1 −/− mice were more susceptible to APAP-induced acute liver injury than wild-type (MsrB1 +/+) mice. Consistent with the in vivo results, primary MsrB1 −/− hepatocytes displayed higher susceptibility to APAP-induced cytotoxicity than MsrB1 +/+ cells. MsrB1 deficiency increased hepatic oxidative stress after APAP challenge such as hydrogen peroxide production, lipid peroxidation, and protein oxidation levels. Additionally, basal and APAP-induced ratios of reduced-to-oxidized GSH (GSH/GSSG) were significantly lower in MsrB1 −/− than in MsrB1 +/+ livers. Nrf2 nuclear accumulation and heme oxygenase-1 expression levels after APAP challenge were lower in MsrB1 −/− than in MsrB1 +/+ livers, suggesting that MsrB1 deficiency attenuates the APAP-induced activation of Nrf2. Collectively, the results of this study suggest that selenoprotein MsrB1 plays a protective role against APAP-induced hepatotoxicity via its antioxidative function.

      PubDate: 2017-10-04T03:45:58Z
      DOI: 10.1016/
  • Evolutionary conservation of EF-hand ΙΙ loop in aequorin: Priority of
           intensity to decay rate in bioluminescence emission
    • Authors: Mahsa Ebrahimi; Ammar Mohseni; Khosrow Khalifeh; Bijan Ranjbar; Reza H. Sajedi
      Abstract: Publication date: Available online 29 September 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Mahsa Ebrahimi, Ammar Mohseni, Khosrow Khalifeh, Bijan Ranjbar, Reza H. Sajedi
      As a Ca2+-regulated photoprotein, aequorin (Aeq) contains four EF-hand motifs, the second one lacks the standard sequence for Ca2+ coordination and doesn't bind to Ca2+. Here, we replaced this loop with a functional loop. According to structural studies, although the global stability of modified aequorin (4EFAeq) is higher than that of Aeq; increasing the local flexibility accompanied by internal structural rearrangements in 4EFAeq result in its penetrability to urea and acrylamide. A fast decay rate was observed for 4EFAeq. Assuming the presence of intermediate states in the luminescent reaction, this observation indicate that the loop replacement leads to the lowering of the half-life of intermediate states which results in increasing the rate of conformational switching of 4EFAeq to light emitting form. However, considerable reduction in initial luminescence intensity of 4EFAeq suggests that the number of functional complexes is reduced. Our findings demonstrate that the conformational effects of the second loop in Aeq elicit a delicate balance between local flexibility and global stability which may be considered as an important functional parameter in photoproteins. It was also concluded that evolutionary conservation of EF-hand ΙΙ in the current form is a consequence of priority of intensity to decay rate in bioluminescent organisms.

      PubDate: 2017-10-04T03:45:58Z
      DOI: 10.1016/
  • A fractionation approach applying chelating magnetic nanoparticles to
           characterize pericardial fluid's proteome
    • Authors: Trindade Paulo; Bastos Adelino Leite-Moreira Bruno Manadas Rita Ferreira Sofia
      Abstract: Publication date: Available online 23 September 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Fábio Trindade, Paulo Bastos, Adelino Leite-Moreira, Bruno Manadas, Rita Ferreira, Sofia F. Soares, Ana L. Daniel-da-Silva, Inês Falcão-Pires, Rui Vitorino
      Owing to their close proximity, pericardial fluid (PF)’s proteome may mirror the pathophysiological status of the heart. Despite this diagnosis potential, the knowledge of PF's proteome is scarce. Large amounts of albumin hamper the characterization of the least abundant proteins in PF. Aiming to expand PF's proteome and to validate the technique for future applications, we have fractionated and characterized the PF, using N-(trimethoxysilylpropyl)ethylenediamine triacetic acid (EDTA)-functionalized magnetic nanoparticles (NPs@EDTA) followed by a GeLC-MS/MS approach. Similarly to an albumin-depletion kit, NPs@EDTA-based fractionation was efficient in removing albumin. Both methods displayed comparable inter-individual variability, but NPs@EDTA outperformed the former with regard to the protein dynamic range as well as to the monitoring of biological processes. Overall, 565 proteins were identified, of which 297 (>50%) have never been assigned to PF. Moreover, owing to this method's good proteome reproducibility, affordability, rapid automation and high binding ability of NP@EDTA, it bears a great potential towards future clinical application.
      Graphical abstract image

      PubDate: 2017-09-26T19:44:48Z
  • All three human scavenger receptor class B proteins can bind and transport
           all three macular xanthophyll carotenoids
    • Authors: Rajalekshmy Shyam; Preejith Vachali; Aruna Gorusupudi; Kelly Nelson; Paul S. Bernstein
      Abstract: Publication date: Available online 23 September 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rajalekshmy Shyam, Preejith Vachali, Aruna Gorusupudi, Kelly Nelson, Paul S. Bernstein
      Carotenoids are plant pigment molecules that are potent antioxidants. Carotenoids cannot be synthesized de novo; therefore, their dietary intake and transport to various tissues are essential to harness their health benefits. Two of the three scavenger receptor class B (SRB) proteins, SR-B1 and CD36, have been implicated as carotenoid transporters in lower species and in various tissues of higher animals. The function of the third SRB protein, SR-B2, in carotenoid transport is unknown. Using surface plasmon resonance (SPR) analyses, we have determined that all three human SRB proteins are capable of binding the macular xanthophyll carotenoids; lutein, zeaxanthin, and meso-zeaxanthin. By over-expressing human SRB proteins in cells that do not endogenously express SRBs, we have determined that lutein uptake is enhanced in the presence of LDL and is mediated by SR-B1 and CD36. SR-B1, SR-B2, and CD36 were able to take up significant amounts of zeaxanthin as well as meso-zeaxanthin, and uptake was increased in the presence of HDL. Our analyses revealed no apparent differences in protein expression profiles of SRBs in central and peripheral regions of human donor tissues, indicating that carotenoid-binding proteins rather than transporters are likely to mediate selective accumulation of carotenoids into the macula.

      PubDate: 2017-09-26T19:44:48Z
      DOI: 10.1016/
  • ATP alters protein folding and function of Escherichia coli uridine
    • Authors: Yi-Kai Liu; Tzu-Hsuan Lin; Pei-Fen Liu
      Abstract: Publication date: Available online 13 September 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yi-Kai Liu, Tzu-Hsuan Lin, Pei-Fen Liu
      Uridine phosphorylase is one of the critical enzymes in the pyrimidine salvage pathway. Cells regenerate uridine for nucleotide metabolism by incorporating uracil with ribose-1-phosphate with this enzyme. Recent studies indicate that Escherichia coli uridine phosphorylase is destabilized in the presence of ATP. However, the mechanism underlying the destabilization process and its influence on uridine phosphorylase function remain to be established. Here, we comprehensively investigated the effects of ATP on protein folding and function of Escherichia coli uridine phosphorylase. Our results demonstrate that ATP apparently decreases the stability of uridine phosphorylase in a concentration-dependent manner. Additionally, simply increasing the level of ATP led to a reduction of enzymatic activity to complete inhibition. Further studies showed that uridine phosphorylase accumulates as a partially unfolded state in the presence of ATP. Moreover, ATP specifically accelerated the unfolding rate of uridine phosphorylase with no observable effects on the refolding process. Our preliminary findings suggest that ATP can alter the protein folding and function of enzymes via apparent destabilization. This mechanism may be significant for proteins functioning under conditions of high levels of ATP, such as cancer cell environments.

      PubDate: 2017-09-15T00:12:36Z
      DOI: 10.1016/
  • Role of ADP ribosylation factor6− Cytohesin1−PhospholipaseD signaling
           axis in U46619 induced activation of NADPH oxidase in pulmonary artery
           smooth muscle cell membrane
    • Authors: Sajal Chakraborti; Jaganmay Sarkar; Animesh Chowdhury; Tapati Chakraborti
      Abstract: Publication date: Available online 16 August 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sajal Chakraborti, Jaganmay Sarkar, Animesh Chowdhury, Tapati Chakraborti
      Treatment of human pulmonary artery smooth muscle cells (HPASMCs) with the thromboxane A2 receptor antagonist, SQ29548 inhibited U46619 stimulation of phospholipase D (PLD) and NADPH oxidase activities in the cell membrane. Pretreatment with apocynin inhibited U46619 induced increase in NADPH oxidase activity. The cell membrane contains predominantly PLD2 along with PLD1 isoforms of PLD. Pretreatment with pharmacological and genetic inhibitors of PLD2, but not PLD1, attenuated U46619 stimulation of NADPH oxidase activity. U46619 stimulation of PLD and NADPH oxidase activities were insensitive to BFA and Clostridium botulinum C3 toxin; however, pretreatment with secinH3 inhibited U46619 induced increase in PLD and NADPH oxidase activities suggesting a major role of cytohesin in U46619-induced increase in PLD and NADPH oxidase activities. Arf-1, Arf-6, cytohesin-1 and cytohesin-2 were observed in the cytosolic fraction, but only Arf-6 and cytohesin-1 were translocated to the cell membrane upon treatment with U46619. Coimmunoprecipitation study showed association of Arf-6 with cytohesin-1 in the cell membrane fraction. In vitro binding of GTPγS with Arf-6 required the presence of cytohesin-1 and that occurs in BFA insensitive manner. Overall, BFA insensitive Arf6−cytohesin1 signaling axis plays a pivotal role in U46619-mediated activation of PLD leading to stimulation of NADPH oxidase activity in HPASMCs.

      PubDate: 2017-08-25T02:59:13Z
      DOI: 10.1016/
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