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BIOCHEMISTRY (230 journals)                  1 2     

Showing 1 - 0 of 0 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Central Science     Hybrid Journal   (Followers: 4)
ACS Chemical Biology     Full-text available via subscription   (Followers: 165)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 15)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 10)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 7)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 8)
Advances in Biological Chemistry     Open Access   (Followers: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 13)
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: 7)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 61)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 13)
American Journal of Polymer Science     Open Access   (Followers: 22)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical Biochemistry     Hybrid Journal   (Followers: 137)
Angiogenesis     Hybrid Journal   (Followers: 2)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 51)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 9)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 43)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 15)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 5)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 22)
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)
Avicenna Journal of Medical Biochemistry     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 19)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 4)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 13)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 25)
Biochemical Pharmacology     Hybrid Journal   (Followers: 7)
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: 220)
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     Full-text available via subscription   (Followers: 15)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 5)
Biochemistry and Molecular Biology of Fishes     Full-text available via subscription   (Followers: 1)
Biochemistry Research International     Open Access   (Followers: 5)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 9)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 16)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 7)
Biochimie     Hybrid Journal   (Followers: 6)
Biochimie Open     Open Access  
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 30)
BioDrugs     Full-text available via subscription   (Followers: 8)
Bioelectrochemistry     Hybrid Journal   (Followers: 1)
Biofuels     Hybrid Journal   (Followers: 10)
Biogeochemistry     Hybrid Journal   (Followers: 11)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 26)
Biomaterials Research     Open Access   (Followers: 3)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Hybrid Journal   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 25)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44)
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: 7)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 5)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 4)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
ChemBioChem     Hybrid Journal   (Followers: 5)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 21)
Chemical Engineering Journal     Hybrid Journal   (Followers: 27)
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: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 29)
Chemistry and Ecology     Hybrid Journal  
ChemTexts     Hybrid Journal  
Clinica Chimica Acta     Hybrid Journal   (Followers: 35)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 19)
Clinical Chemistry     Full-text available via subscription   (Followers: 68)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 63)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 5)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 7)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 3)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 9)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 4)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 14)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 21)
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: 58)
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: 3)
Frontiers in Molecular Biosciences     Open Access   (Followers: 2)
Frontiers in Natural Product Chemistry     Hybrid Journal  
Global Biogeochemical Cycles     Full-text available via subscription   (Followers: 11)
Green Chemistry     Full-text available via subscription   (Followers: 8)
Histochemistry and Cell Biology     Hybrid Journal   (Followers: 4)
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: 7)
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: 5)
International Journal of Food Contamination     Open Access  
International Journal of Plant Physiology and Biochemistry     Open Access  
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: 1)
Journal of Applied Biology & Biotechnology     Open Access   (Followers: 1)
Journal of Bioactive and Compatible Polymers     Hybrid Journal   (Followers: 2)
Journal of Biochemistry     Hybrid Journal   (Followers: 42)
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 166)
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: 1)
Journal of Chemical Neuroanatomy     Hybrid Journal  
Journal of Clinical Lipidology     Hybrid Journal   (Followers: 1)
Journal of Comparative Physiology B : Biochemical, Systemic, and Environmental Physiology     Hybrid Journal   (Followers: 4)
Journal of Drug Discovery and Therapeutics     Open Access   (Followers: 1)
Journal of Enzyme Inhibition and Medicinal Chemistry     Hybrid Journal   (Followers: 4)
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: 3)
Journal of Inborn Errors of Metabolism and Screening     Open Access  
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Investigational Biochemistry     Open Access   (Followers: 2)
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: 3)
Journal of Nutritional Biochemistry     Hybrid Journal   (Followers: 7)
Journal of Pediatric Biochemistry     Hybrid Journal   (Followers: 1)
Journal of Peptide Science     Hybrid Journal   (Followers: 24)
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: 5)
Journal of Steroid Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Journal of Virology & Antiviral Research     Hybrid Journal   (Followers: 3)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 7)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Lab on a Chip     Full-text available via subscription   (Followers: 34)
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: 4)
Molecular Aspects of Medicine     Hybrid Journal   (Followers: 4)
Molecular Informatics     Hybrid Journal   (Followers: 5)
Molecular inhibitors in targeted therapy     Open Access  
Moscow University Chemistry Bulletin     Hybrid Journal   (Followers: 1)
Mycology : An International Journal on Fungal Biology     Hybrid Journal   (Followers: 4)
Natural Products and Bioprospecting     Open Access   (Followers: 3)
Nature Chemical Biology     Full-text available via subscription   (Followers: 65)
Nature Communications     Open Access   (Followers: 103)
Neurosignals     Open Access   (Followers: 2)
Novelty in Biomedicine     Open Access  
Ocean Acidification     Open Access   (Followers: 2)
Organic & Biomolecular Chemistry     Full-text available via subscription   (Followers: 83)
Peptidomics     Open Access  
Pesticide Biochemistry and Physiology     Hybrid Journal   (Followers: 4)
Pflugers Archiv European Journal of Physiology     Hybrid Journal   (Followers: 3)
Pharmaceutical Bioprocessing     Full-text available via subscription   (Followers: 1)
Pharmacognosy Magazine     Open Access   (Followers: 2)

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.478]   [H-I: 138]   [22 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [3039 journals]
  • Physico-chemical characteristics and primary structure of an
           affinity-purified α-D-galactose-specific, jacalin-related lectin from the
           latex of mulberry (Morus indica)
    • Abstract: Publication date: Available online 21 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Debparna Datta, Gottfried Pohlentz, Mona Schulte, Mathias Kaiser, Francisco M. Goycoolea, Johannes Müthing, Michael Mormann, Musti J. Swamy
      An α-D-galactose specific lectin belonging to the family of jacalin-related lectins (JRL) has been purified by affinity chromatography on cross-linked guar-gum. Mass spectrometric data suggested that the protein harbors two chains like all the members of galactose-specific jacalin-related lectins (gJRL). De novo sequencing of proteolytic peptides demonstrated that the heavier chain consists of 133 amino acids and the lighter chain comprises of 21 or 24 amino acids. The heavier chain contains one N-glycosylation site (Asn47) occupied with either pauci-mannose type [GlcNAc2(Fuc)Man3(Xyl)] or complex type [GlcNAc2(Fuc)Man3(Xyl)GlcNAc(Fuc)Gal] N-glycans. Circular dichroism spectroscopy indicated that the secondary structure of the lectin is predominantly made up of β-sheets, and differential scanning calorimetry revealed a thermal denaturation temperature of 77.6 °C. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assays on MCF-7 and MDCK cells showed that the lectin is highly cytotoxic towards both cell lines when dosed at micromolar concentrations, suggesting that it may play a role in the defense mechanism of the plant.

      PubDate: 2016-09-21T15:25:50Z
  • The propensity for tropomyosin twisting in the presence and absence of
    • Abstract: Publication date: Available online 20 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Michael J. Rynkiewicz, Stefan Fischer, William Lehman
      A canonical model of muscle α-tropomyosin (Tpm1.1), based on molecular-mechanics and electron microscopy of different contractile states, shows that the two-stranded coiled-coiled is pre-bent to present a specific molecular-face to the F-actin filament. This conformation is thought to facilitate both filament assembly and tropomyosin sliding across actin to modulate myosin-binding. However, to bind effectively to actin filaments, the 42 nm-long tropomyosin coiled-coil is not strictly canonical. Here, the mid-region of tropomyosin twists an additional ∼20° in order to better match the F-actin helix. In addition, the N- and C-terminal regions of tropomyosin polymerize head-to-tail to form continuous super-helical cables. In this case, 9 to 10 residue-long overlapping domains between adjacent molecules untwist relative to each other to accommodate orthogonal interactions between chains in the junctional four-helix nexus. Extensive molecular dynamics simulations show that the twisting and untwisting motions of tropomyosin vary appreciably along tropomyosin length, and in particular that substantial terminal domain winding and unwinding occurs whether tropomyosin is bound to F-actin or not. The local and regional twisting and untwisting do not appear to proceed in a concerted fashion, resembling more of a “wringing-type” behavior rather than a rotation.
      Graphical abstract image

      PubDate: 2016-09-21T15:25:50Z
  • RKIP suppresses the proliferation and metastasis of breast cancer cell
           lines through up-regulation of miR-185 targeting HMGA2
    • Abstract: Publication date: Available online 17 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Qiongyan Zou, Haijun Wu, Fenfen Fu, Wenjun Yi, Lei Pei, Meirong Zhou
      Raf-1 kinase inhibitor protein (RKIP) is a tumor and metastasis suppressor in cancer cells. MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. In this study, we found the expression of RKIP and miR-185 in breast cancer tissues was significantly lower than that of in normal breast tissues. Over-expression of RKIP up-regulated miR-185 expression, inhibited breast cancer cell growth and invasion, and inhibited miR-185 target gene High-mobility group AT-hook 2 (HMGA2). HMGA2 is encoded by HMGA2 gene, which encodes a protein that belongs to the non-histone chromosomal high-mobility group (HMG) protein family. Moreover, RKIP knockdown attenuated the inhibition of breast cancer cell invasion and the expression of HMGA2 by miR-185. Forced HMGA2 overexpression could partly restore the inhibitory effect of miR-185 on breast cancer cell growth and invasion. Our findings newly described RKIP/miR-185 to HMGA2 link and provided a potential mechanism for breast cancer cell growth and invasion. It may illustrate the potential therapeutic utility of signaling pathway signatures.

      PubDate: 2016-09-21T15:25:50Z
  • Biochemical and structural characterization of quinoprotein aldose sugar
           dehydrogenase from Thermus thermophilus HJ6: Mutational analysis of Tyr156
           in the substrate-binding site
    • Abstract: Publication date: 15 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 608
      Author(s): Han-Woo Kim, Ji-Yeon Wang, Ji-Yeon Lee, Ae-Kyung Park, Hyun Park, Sung-Jong Jeon
      The gene encoding a quinoprotein aldose sugar dehydrogenase (ASD) from Thermus thermophilus HJ6 (Tt_ASD) was cloned and sequenced; it comprised 1059 nucleotides encoding a protein containing 352 amino acids that had a predicted molecular mass of 38.9 kDa. The deduced amino acid sequence showed 42.9% and 33.9% identities to the ASD proteins from Pyrobaculum aerophilum and Escherichia coli, respectively. The biochemical properties of Tt_ASD were characterized. The optimum pH for the oxidation of glucose was 7.0–7.5 and the optimum temperature was 70 °C. The half-life of heat inactivation for the apoenzyme was about 25 min at 85 °C. The enzyme was highly thermostable, and the activity of the pyrroloquinoline quinone-bound holoenzyme was not lost after incubation at 85 °C for 100 min. Tt_ASD could oxidize various sugars, including hexoses, pentoses, disaccharides, and polysaccharides, in addition to alcohols. Structural analysis suggested that Tyr156 would be the substrate-binding residue. Two mutants, Y156A and Y156K, had impaired activities and affinities for all substrates and completely lost their activities for alcohols. This structural and mutational analysis of Tt_ASD demonstrates the crucial role of Tyr156 in determining substrate specificity.
      Graphical abstract image

      PubDate: 2016-09-15T14:57:26Z
  • Appraisal of role of the polyanionic inducer length on amyloid formation
           by 412-residue 1N4R Tau protein: A comparative study
    • Abstract: Publication date: Available online 13 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Abolfazl Jangholi, Mohammad Reza Ashrafi-Kooshk, Seyed Shahriar Arab, Gholamhossein Riazi, Farzad Mokhtari, Mansour Poorebrahim, Hamid Mahdiuni, Boris I. Kurganov, Ali Akbar Moosavi-Movahedi, Reza Khodarahmi
      In many neurodegenerative diseases, formation of protein fibrillar aggregates has been observed as a major pathological change. Neurofibrillary tangles, mainly composed of fibrils formed by the microtubule-associated protein; Tau, are a hallmark of a group of neurodegenerative diseases such as Alzheimer's disease. Tau belongs to the class of natively unfolded proteins and partially folds into an ordered β-structure during aggregation. Polyanionic cofactors such as heparin are commonly used as inducer of Tau aggregation in vitro. The role of heparin in nucleation and elongation steps during Tau fibril formation is not fully understood. In the current study, aggregation kinetics as well as structure of Tau amyloid fibrils, by using the 1N4R isoform, have been reproducibly determined in the presence of heparin and the shorter molecule; enoxaparin. The kinetic studies demonstrated that heparin (not enoxaparin) efficiently accelerates Tau amyloid formation and revealed, mechanistically, that the molecular weight of the inducer is important in accelerating amyloidogenesis. The kinetic parameter values of Tau amyloid aggregation, especially, the amyloid aggregation extent, were relatively different in the presence of heparin and enoxaparin, at various stoichiometries of the inducers binding. Also, based on the results, obtained from CD, FTIR, AFM and XRD studies, it may be suggested that the inducer length plays a critical role mainly in the nucleation process, so that it determines that oligomers lie on or off the pathway of Tau fibrillization. The biochemical results herein suggest that the chemical environment of the extracellular matrix as well as localization of distinct glycosaminoglycans may influence deposition behavior of Tau amyloidosis.
      Graphical abstract image

      PubDate: 2016-09-15T14:57:26Z
  • Editorial: The Cutting Edge of Zinc Biology
    • Abstract: Publication date: Available online 15 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Taiho Kambe, Toshiyuki Fukada, Shinya Toyokuni

      PubDate: 2016-09-15T14:57:26Z
  • Redox status in a model of cancer stem cells
    • Abstract: Publication date: Available online 13 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Mattia Zaccarin, Valentina Bosello-Travain, Maria Luisa Di Paolo, Marco Falda, Matilde Maiorino, Giovanni Miotto, Stefano Piccolo, Antonella Roveri, Fulvio Ursini, Rina Venerando, Stefano Toppo
      Reversible oxidation of Cys residues is a crucial element of redox homeostasis and signaling. According to a popular concept in oxidative stress signaling, the oxidation of targets of signals can only take place following an overwhelming of the cellular antioxidant capacity. This concept, however, ignores the activation of feedback mechanisms possibly leading to a paradoxical effect. In a model of cancer stem cells (CSC), stably overexpressing the TAZ oncogene, we observed that the increased formation of oxidants is associated with a globally more reduced state of proteins. Redox proteomics revealed that several proteins, capable of undergoing reversible redox transitions, are indeed more reduced while just few are more oxidized. Among the proteins more oxidized, G6PDH emerges as both more expressed and activated by oxidation. This accounts for the observed more reduced state of the NADPH/NADP+ couple. The dynamic redox flux generating this apparently paradoxical effect is rationalized in a computational system biology model highlighting the crucial role of G6PDH activity on the rate of redox transitions eventually leading to the reduction of reversible redox switches.

      PubDate: 2016-09-15T14:57:26Z
  • ATF4 regulates arsenic trioxide-mediated NADPH oxidase, ER-mitochondrial
           crosstalk and apoptosis
    • Abstract: Publication date: Available online 13 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ritesh K. Srivastava, Changzhao Li, Aftab Ahmad, Onika Abrams, Marina S. Gorbatyuk, Kevin S. Harrod, Ronald C. Wek, Farrukh Afaq, Mohammad Athar
      Arsenic is a mitochondrial toxin, and its derivatives, such as arsenic trioxide (ATO), can trigger endoplasmic reticulum (ER) and the associated unfolded protein response (UPR). Here, we show that arsenic induction of the UPR triggers ATF4, which is involved in regulating this ER-mitochondrial crosstalk that is important for the molecular pathogenesis of arsenic toxicity. Employing ATF4 +/+ and ATF4 −/− MEFs, we show that ATO induces UPR and impairs mitochondrial integrity in ATF4 +/+ MEF cells which is largely ablated upon loss of ATF4. Following ATO treatment, ATF4 activates NADPH oxidase by promoting assembly of the enzyme components Rac-1/P47phox/P67phox, which generates ROS/superoxides. Furthermore, ATF4 is required for triggering Ca++/calpain/caspase-12-mediated apoptosis following ATO treatment. The IP3R inhibitor attenuates Ca++/calpain-dependent apoptosis, as well as reduces m-ROS and MMP disruption, suggesting that ER-mitochondria crosstalk involves IP3R-regulated Ca++ signaling. Blockade of m-Ca++ entry by inhibiting m-VDAC reduces ATO-mediated UPR in ATF4 +/+ cells. Additionally, ATO treatment leads to p53-regulated mitochondrial apoptosis, where p53 phosphorylation plays a key role. Together, these findings indicate that ATO-mediated apoptosis is regulated by both ER and mitochondria events that are facilitated by ATF4 and the UPR. Thus, we describe novel mechanisms by which ATO orchestrates cytotoxic responses involving interplay of ER and mitochondria.
      Graphical abstract image

      PubDate: 2016-09-15T14:57:26Z
  • Nucleotide-free kinesin motor domains reversibly convert to an inactive
           conformation with characteristics of a molten globule
    • Abstract: Publication date: 15 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 608
      Author(s): David D. Hackney, Marshall S. McGoff
      Nucleotide-free kinesin motor domains from several kinesin families convert reversibly to a refractory conformation that cannot rapidly rebind ADP. In the absence of glycerol, the refractory conformation of Drosophila kinesin motor domains is favored by 50-fold with conversion of the active to the refractory species at ∼0.052 s−1 and reactivating in the presence of ADP at ∼0.001 s−1. This reactivation by ADP is due to conformational selection rather than induced fit because ADP is not bound to the refractory species at concentrations of ADP that are sufficient to saturate the rate of reactivation. Glycerol stabilizes the active conformation by reducing the rate of inactivation, while having little effect on the reactivation rate. Circular dichroism indicates a large conformational change occurs on formation of the refractory species. The refractory conformation binds ANS (8-anilino-1-napthalenesulfonic acid) with a large increase in fluorescence, indicating that it has molten globule character. High ANS binding is also observed with the refractory forms of Eg5 (a kinesin-5) and Ncd (a kinesin-14), indicating that a refractory conformation with molten globule characteristics may be a common feature of nucleotide-free kinesin motor domains.
      Graphical abstract image

      PubDate: 2016-09-15T14:57:26Z
  • Nodal signaling modulates the expression of Oct-4 via nuclear
           translocation of β-catenin in lung and prostate cancer cells
    • Abstract: Publication date: 15 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 608
      Author(s): Yi-Fei Qi, Long Wu, Zi-Qian Li, Meng-Ling Wu, Hai-Fang Wang, Ka-Ying Chan, Lin-Lin Lu, Shao-Hui Cai, Hong-Sheng Wang, Jun Du
      Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation. This increase was attributed to GSK-3β dephosphorylating, and activin receptor-like kinase 4/7 (ALK4/7) played a major role in human cancer cells. Our study provides a positive understanding of Nodal function in cancer cells and suggests a potential novel target for clinical therapeutic research.
      Graphical abstract image

      PubDate: 2016-09-15T14:57:26Z
  • CD147 induces up-regulation of vascular endothelial growth factor in
           U937-derived foam cells through PI3K/AKT pathway
    • Abstract: Publication date: Available online 9 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): JiaXin Zong, YunTian Li, DaYong Du, Yang Liu, YongJun Yin
      Intraplaque angiogenesis has been recognized as an important risk factor for the rupture of advanced atherosclerotic plaques in recent years. CD147, also called Extracellular Matrix Metalloproteinase Inducer, has been found the ability to promote angiogenesis in many pathological conditions such as cancer diseases and rheumatoid arthritis via the up-regulation of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis. We investigated whether CD147 would also induce the up-regulation of VEGF in the foam cells formation process and explored the probable signaling pathway. The results showed the expression of CD147 and VEGF was significantly higher in U937-derived foam cells. After CD147 stealth siRNA transfection treatment, the production of VEGF was reduced depended on the inhibition efficiency of CD147 siRNAs.The special signaling pathway inhibitors LY294002, SP600125, SB203580 and U0126 were added to cultures respectively and the results showed LY294002 dose-dependently inhibited the expression of VEGF. The reduction of phospho-Akt was observed in both LY294002 and siRNA groups, suggested that the phosphatidylinositol 3-kinase/Akt pathway may be the probable signaling pathway underlying CD147 induced up-regulation of VEGF in U937-derived foam cells.

      PubDate: 2016-09-10T14:43:56Z
  • Structural studies of N-terminal mutants of Connexin 26 and Connexin 32
           using 1H NMR spectroscopy
    • Abstract: Publication date: 15 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 608
      Author(s): Yuksel Batir, Thaddeus A. Bargiello, Terry L. Dowd
      Alterations in gap junctions underlie the etiologies of syndromic deafness (KID) and Charcot-Marie Tooth disease (CMTX). Functional gap junctions are composed of connexin molecules with N-termini containing a flexible turn around G12, inserting the N-termini into the channel pore allowing voltage gating. The loss of this turn correlates with loss of Connexin 32 (Cx32) function by impaired trafficking to the cell membrane. Using 1H NMR we show the N-terminus of a syndromic deafness mutation Cx26G12R, producing “leaky channels”, contains a turn around G12 which is less structured and more flexible than wild-type. In contrast, the N-terminal structure of the same mutation in Cx32 chimera, Cx32*43E1G12R shows a larger constricted turn and no membrane current expression but forms membrane inserted hemichannels. Their function was rescued by formation of heteromeric channels with wild type subunits. We suggest the inflexible Cx32G12R N-terminus blocks ion conduction in homomeric channels and this channel block is relieved by incorporation of wild type subunits. In contrast, the increased open probability of Cx26G12R hemichannels is likely due to the addition of positive charge in the channel pore changing pore electrostatics and impairing hemichannel regulation by Ca2+. These results provide mechanistic information on aberrant channel activity observed in disease.

      PubDate: 2016-09-10T14:43:56Z
  • Inhibitory effects of cold atmospheric plasma on the growth, ergosterol
           biosynthesis, and keratinase activity in Trichophyton rubrum
    • Abstract: Publication date: 15 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 608
      Author(s): Atena Shapourzadeh, Neda Rahimi-Verki, Seyed-Mohammad Atyabi, Masoomeh Shams-Ghahfarokhi, Zahra Jahanshiri, Shiva Irani, Mehdi Razzaghi-Abyaneh
      Background Dermatophytosis is the most important superficial fungal infection which affects nearly 20% of human population worldwide. Recurrence of disease and emerging resistance of Trichophyton rubrum to synthetic antifungals are the main problems in control of dermatophytosis. The purpose of this study was to evaluate the effect of cold atmospheric plasma (CAP) on T. rubrum growth, ergosterol biosynthesis and keratinase activity. Methods A CAP system, comprised of helium 98% – oxygen 2% (He/O2), was used. Trichophyton rubrum conidia suspensions were treated with CAP in time periods of 90, 120, 150 and 180 s in 96-well microplates. Fungal growth was evaluated by counting the colony forming unit (CFU). Fungal dry weight, ergosterol biosynthesis and keratinase activity were evaluated in CAP-treated T. rubrum and untreated controls. Results T. rubrum growth was significantly inhibited by 62%–91%. CAP strongly suppressed fungal ergosterol biosynthesis by 27%–54%. The keratinase activity was increased by 7.30%–21.88% up to 120 s CAP exposure. Conclusion Our results demonstrated for the first time that CAP inhibits T. rubrum growth, suppresses ergosterol biosynthesis and increases moderately keratinase activity in a dose-dependent manner. Overall, CAP exposure could be a potentially useful method for treatment of clinical cases of human and animal dermatophytoses.

      PubDate: 2016-09-10T14:43:56Z
  • Resolving the 3D spatial orientation of helix I in the closed state of the
           colicin E1 channel domain by FRET. Insights into the integration mechanism
    • Abstract: Publication date: Available online 3 September 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Miguel R. Lugo, Derek Ho, A. Rod Merrill
      Current evidence suggests that the closed-state membrane model for the channel-forming domain of colicin E1 involves eight amphipathic α-helices (helices I–VII and X) that adopt a two-dimensional arrangement on the membrane surface. Two central hydrophobic α-helices in colicin E1 (VIII and IX) adopt a transmembrane location–the umbrella model. Helices I and II have been shown to participate in the channel by forming a transmembrane segment (TM1) in the voltage-induced open channel state. Consequently, it is paramount to determine the relative location and orientation of helix I in the two-dimensional arrangement of the membrane. A new, low-resolution, three-dimensional model of the closed state of the colicin E1 channel was constructed based on FRET measurements between three naturally occurring Trp residues and three sites in helix I, in addition to previously reported FRET distances for the channel domain. Furthermore, a new mechanism for the channel integration process involving the transition of the soluble to membrane-bound form is presented based on a plethora of kinetic data for this process.

      PubDate: 2016-09-05T14:35:27Z
  • Protection from ischemia by preconditioning, postconditioning, and
           combined treatment in rabbit testicular ischemia reperfusion injury
    • Abstract: Publication date: Available online 29 August 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Xiaoying Zhang, Fangqing Lv, Jie Tang
      This study aimed to investigate the protection of ischemic preconditioning (IPreC), ischemic postconditioning (IPostC) and combined treatment on ischemia reperfusion injury (IRI) of testis. A rabbit testicular ischemia reperfusion (IR) model was established with determining of rabbit serum testosterone, nitric oxide (NO), malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), and tissues pathology. After IR, the NO, MDA, PC, SOD, MPO, and GSH-Px expression significantly increased in torsive testis, and significantly decreased after IPreC, IPostC, and combined treatment in torsive testis when compared to contralateral testis. In torsive testis, testicular tissues was severely damaged with spermatogenic cells disappearing, and were filled with light eosin edema liquid. Cell apoptosis index significantly increased, and the ratio of Bcl-2/Bax significantly decreased. After IPreC, IPostC, and combined treatment, testicular tissues were restored to normal, cell apoptosis index significantly decreased, and the ratio of Bcl-2/Bax significantly increased. It indicates that IPreC, IPostC, and combined treatment has an obvious protective effect on testicular IRI, by decreasing the oxidative stress index and cell apoptosis, provides a significant reference for the treatment of testicular torsion induced infertility, and exhibits a great value in clinical applications.

      PubDate: 2016-08-31T23:35:06Z
  • Experimental and computational studies on the unusual substrate
           specificity of branched-chain amino acid aminotransferase from
           Thermoproteus uzoniensis
    • Abstract: Publication date: 1 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 607
      Author(s): Ekaterina Yu. Bezsudnova, Tatiana N. Stekhanova, Dmitry A. Suplatov, Andrey V. Mardanov, Nikolai V. Ravin, Vladimir O. Popov
      PLP-Dependent fold-type IV branched-chain amino acid aminotransferases (BCATs) from archaea have so far been poorly characterized. A new BCAT from the hyperthermophilic archaeon Thermoproteus uzoniensis (TUZN1299) has been studied. TUZN1299 was found to be highly active toward branched-chain amino acids (BCAAs), positively charged amino acids, l-methionine, l-threonine, l-homoserine, l-glutamine, as well as toward 2-oxobutyrate and keto analogs of BCAAs, whereas l-glutamate and α-ketoglutarate were not converted in the overall reaction. According to stopped-flow experiments, the enzyme showed the highest specificity to BCAAs and their keto analogs. In order to explain the molecular mechanism of the unusual specificity of TUZN1299, bioinformatic analysis was implemented to identify the subfamily-specific positions in the aminotransferase class IV superfamily of enzymes. The role of the selected residues in binding of various ligands in the active site was further studied using molecular modeling. The results indicate that Glu188 forms a novel binding site for positively charged and polar side-chains of amino acids. Lack of accommodation for α-ketoglutarate and l-glutamate is due to the unique orientation and chemical properties of residues 102–106 in the loop forming the A-pocket. The likely functional roles of TUZN1299 in cellular metabolism – in the synthesis and degradation of BCAAs – are discussed.
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      PubDate: 2016-08-31T23:35:06Z
  • Inhibition of autophagy enhances heat-induced apoptosis in human non-small
           cell lung cancer cells through ER stress pathways
    • Abstract: Publication date: Available online 24 August 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Wen-Yue Xie, Xiang-Dong Zhou, Juan Yang, Ling-Xiu Chen, Dan-Hua Ran
      The occurrence and mechanisms of autophagy induced by heat stress are not well known in lung cancer cells. Here, we have demonstrated that heat stress induces autophagy in A549 and NCI-H460 cells through morphological and biochemical analyses. The inhibition of autophagy by chloroquine, 3-methyladenine and Beclin 1 siRNA enhanced heat-induced apoptosis. Moreover, the combination of chloroquine and heat stress inhibited tumor growth and enhanced apoptosis in vivo experiments. In addition, heat-induced autophagy involved the ER stress pathway (PERK- or IRE1-dependent). Further, heat treatment led to the increased phosphorylation of AMPK and the decreased phosphorylation of mTOR in vitro and in vivo. Knockdown of GRP78 inhibited the AMPK-mTOR pathway, and the AMPK inhibitor compound C decreased heat-induced autophagy, suggesting that activation of ER stress was involved in autophagy induction and promotion of the AMPK-mTOR pathway. In conclusion, our data suggested that the heat treatment of lung cancer cells triggered protective autophagy, as mediated by ER stress. Thus, inhibition of autophagy can be a promising strategy to enhance hyperthermia in the treatment of lung cancer patients.
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      PubDate: 2016-08-26T15:38:19Z
  • Cyclic tensile strain promotes the osteogenic differentiation of a bone
           marrow stromal cell and vascular endothelial cell co-culture system
    • Abstract: Publication date: Available online 22 August 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yunan Jiang, Yu Wang, Guohua Tang
      Mechanical stimuli and neovascularization are closely coupled to osteogenic differentiation and new bone formation. The purpose of present study was to detect the effect of cyclic mechanical strain on a co-culture system of bone marrow stromal cells (BMSCs) and vascular endothelial cells (VECs) and to clarify the related mechanisms. Primary BMSCs and VECs were isolated from Sprague-Dawley rats and co-cultured at various ratios (1:0, 1:2, 1:4, 4:1, 2:1, 1:1, and 0:1). To determine optimized loading conditions, the cells were then subjected to various cyclic tensile strains (0%, 3%, 6% and 9%) using a Flexcell 5000 mechanical loading system. A protocol of 6% strain on the co-cultured cells at a 1:1 ratio was selected as the optimized culture conditions based on the best osteogenic effects, which included increased ALP activity, matrix mineralization and the expressions of VEGF, Runx-2 and Col-1. The VEGF-R inhibitor tivozanib was used to analyze the paracrine role of VEGF, and the osteogenesis-promoting effects of 6% tensile strain were abrogated in the co-cultured cells treated with tivozanib. These results demonstrate that cyclic tensile strain promotes osteogenic differentiation in BMSC/VEC co-culture systems, possibly via a VEC-mediated paracrine effect of VEGF on BMSCs.

      PubDate: 2016-08-26T15:38:19Z
  • Calcium sensing receptor effects in adipocytes and liver cells:
           Implications for an adipose-hepatic crosstalk
    • Abstract: Publication date: Available online 24 August 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Pia Villarroel, Pamela Mattar, Amanda D'Espessailles, Marco Arrese, Andrea Arreguin, Cecilia Fuentes, Marcela Reyes, Mariana Cifuentes
      The calcium sensing receptor (CaSR) is expressed in human adipose cells, and its activation may associate with adipose tissue (AT) dysfunction. We evaluated whether CaSR stimulation influences adipocyte triglyceride (TG) and fatty acid binding protein 4 (aP2) content, and hepatocyte TGs and proinflammatory cytokine expression. The effect of the calcimimetic cinacalcet on TGs (fluorimetry), lipogenic genes (qPCR) and aP2 (immunoblot) was evaluated in LS14 adipocytes or AT. In the human HepG2 hepatic cell line, we assessed CaSR expression and cinacalcet effect on TGs and lipogenic and proinflammatory genes. CaSR activation decreased adipocyte TG content by 20% and the expression of GPD and LPL by 34% and 20%, respectively. Cinacalcet increased aP2 protein expression by 60%. CaSR expression was shown in HepG2 cells and human liver samples. Cinacalcet-treated HepG2 cells in the presence of oleic acid exhibited a19% increased TG content. No changes were observed in the expression of lipogenic genes in HepG2 cells, however there was a 50%–300% elevation in the expression of proinflammatory cytokines. CaSR activation in adipocytes may associate with decreased TG storage ability and increased aP2. Hepatic CaSR stimulation may elevate steatosis and proinflammatory factors. We propose that CaSR may contribute to obesity-associated hepatic metabolic consequences.

      PubDate: 2016-08-26T15:38:19Z
  • Bioassay-guided isolation of dehydrocostus lactone from Saussurea lappa: A
           new targeted cytosolic thioredoxin reductase anticancer agent
    • Abstract: Publication date: Available online 18 August 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Meili Yang, Junmin Zhang, Ya Li, Xiao Han, Kun Gao, Jianguo Fang
      In a screen for mammalian thioredoxin reductases inhibitors, an MeOH extract from the roots of Saussurea lappa C.B. Clarke (Compositae) inhibited the activity of cytosolic thioredoxin reductase (TrxR1). Bioassay-guided separation of the extract led to the isolation of a new TrxR1 inhibitor, dehydrocostus lactone (DHC), a guaiane-type sesquiterpene. The content of DHC in the extract was determined to be 0.4%. DHC inhibited human cervical carcinoma HeLa cells with an IC50 of ∼12.00 μM but displayed less cytotoxicity to human immortalized normal liver cells L02. We observed that DHC killed HeLa cells through induction of apoptosis. DHC inhibited the activity of TrxR1 in HeLa cells, which elicited an accumulation of reactive oxygen species (ROS) in cells and a collapse of the intracellular redox equilibrium and eventually induced apoptosis of HeLa cells.
      Graphical abstract image

      PubDate: 2016-08-21T15:25:46Z
  • The effect of introducing small cavities on the allosteric inhibition of
           phosphofructokinase from Bacillus stearothermophilus
    • Abstract: Publication date: 1 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 607
      Author(s): Amy M. Whitaker, Gregory D. Reinhart
      The allosteric coupling free energy between ligands fructose-6-phosphate (Fru-6-P) and phospho(enol)pyruvate (PEP) for phosphofructokinase-1 (PFK) from the moderate thermophile, Bacillus stearothermophilus (BsPFK), results from compensating enthalpy and entropy components. In BsPFK the positive coupling free energy that defines inhibition is opposite in sign from the negative enthalpy term and is therefore determined by the larger absolute value of the negative entropy term. Variants of BsPFK were made to determine the effect of adding small cavities to the structure on the allosteric function of the enzyme. The BsPFK Ile → Val (cavity containing) mutants have varied values for the coupling free energy between PEP and Fru-6-P, indicating that the modifications altered the effectiveness of PEP as an inhibitor. Notably, the mutation I153V had a substantial positive impact on the magnitude of inhibition by PEP. Van't Hoff analysis determined that this is the result of decreased entropy-enthalpy compensation with a larger change in the enthalpy term compared to the entropy term.

      PubDate: 2016-08-21T15:25:46Z
  • Mitochondrial nitric oxide production supported by reverse electron
    • Abstract: Publication date: 1 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 607
      Author(s): Silvina S. Bombicino, Darío E. Iglesias, Tamara Zaobornyj, Alberto Boveris, Laura B. Valdez
      Heart phosphorylating electron transfer particles (ETPH) produced NO at 1.2 ± 0.1 nmol NO. min−1 mg protein−1 by the mtNOS catalyzed reaction. These particles showed a NAD+ reductase activity of 64 ± 3 nmol min−1 mg protein−1 sustained by reverse electron transfer (RET) at expenses of ATP and succinate. The same particles, without NADPH and in conditions of RET produced 0.97 ± 0.07 nmol NO. min−1 mg protein−1. Rotenone inhibited NO production supported by RET measured in ETPH and in coupled mitochondria, but did not reduce the activity of recombinant nNOS, indicating that the inhibitory effect of rotenone on NO production is due to an electron flow inhibition and not to a direct action on mtNOS structure. NO production sustained by RET corresponds to 20% of the total amount of NO released from heart coupled mitochondria. A mitochondrial fraction enriched in complex I produced 1.7 ± 0.2 nmol NO. min−1 mg protein−1 and reacted with anti-75 kDa complex I subunit and anti-nNOS antibodies, suggesting that complex I and mtNOS are located contiguously. These data show that mitochondrial NO production can be supported by RET, and suggest that mtNOS is next to complex I, reaffirming the idea of a functional association between these proteins.
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      PubDate: 2016-08-21T15:25:46Z
  • Magnesium cations assist with unpairing hydrogen-bonded 2-deoxyribose
    • Abstract: Publication date: Available online 20 August 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Alexander A. Tulub
      2-deoxyribose trinucleotides are essential units for storage and transfer of the genetic information. Nucleotide transpositions in trinucleotide sequences affect production of different amino acids. The study focuses on the mechanism of unpairing initially H-bonded trinucleotides. In living cells, the unpairing proceeds through DNA polymerase operating only in the presence of Mg cations. The DNA polymerase is a very complex system to be studied quantum chemically. In our simplistic approach, the polymerase is replaced by two Mg cations attached to both sides of the complementary trinucleotides. A distinguished feature of Mg in cell is in its easiness to accept and donate the electron density. In a particular molecular configuration, this makes Mg singly charged. As to the current case, we observe an unpaired electron on the Mg+ and an unpaired electron on the trinucleotide − totally, a radical pair which coupling produces either triplet or singlet state. The study, based on the DFT B3LYP (6-311G** basis set) computations, shows that the singlet state energetically is less preferable than the triplet state. The latter is unstable and makes the trinucleotide strands unpair in the region where the singlet and triplet states cross.

      PubDate: 2016-08-21T15:25:46Z
  • Corrigendum to “What is the concentration of hydrogen peroxide in blood
           and plasma'” [Arch. Biochem. Biophys. 603 (2016) 48–53]
    • Abstract: Publication date: 1 October 2016
      Source:Archives of Biochemistry and Biophysics, Volume 607
      Author(s): Henry Jay Forman, Angelito Bernardo, Kelvin J.A. Davies

      PubDate: 2016-08-21T15:25:46Z
  • Identification of structural determinants of NAD(P)H selectivity and
           lysine binding in lysine N6-monooxygenase
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Heba Abdelwahab, Reeder Robinson, Pedro Rodriguez, Camelia Adly, Sohby El-Sohaimy, Pablo Sobrado
      l-lysine (l-Lys) N 6-monooxygenase (NbtG), from Nocardia farcinica, is a flavin-dependent enzyme that catalyzes the hydroxylation of l-Lys in the presence of oxygen and NAD(P)H in the biosynthetic pathway of the siderophore nocobactin. NbtG displays only a 3-fold preference for NADPH over NADH, different from well-characterized related enzymes, which are highly selective for NADPH. The structure of NbtG with bound NAD(P)+ or l-Lys is currently not available. Herein, we present a mutagenesis study targeting M239, R301, and E216. These amino acids are conserved and located in either the NAD(P)H binding domain or the l-Lys binding pocket. M239R resulted in high production of hydrogen peroxide and little hydroxylation with no change in coenzyme selectivity. R301A caused a 300-fold decrease on k cat/K m value with NADPH but no change with NADH. E216Q increased the K m value for l-Lys by 30-fold with very little change on the k cat value or in the binding of NAD(P)H. These results suggest that R301 plays a major role in NADPH selectivity by interacting with the 2′-phosphate of the adenine-ribose moiety of NADPH, while E216 plays a role in l-Lys binding.
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      PubDate: 2016-08-16T15:00:32Z
  • I86A/C295A mutant secondary alcohol dehydrogenase from Thermoanaerobacter
           ethanolicus has broadened substrate specificity for aryl ketones
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Christopher M. Nealon, Travis P. Welsh, Chang Sup Kim, Robert S. Phillips
      Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase (SADH) reduces aliphatic ketones according to Prelog's Rule, with binding pockets for small and large substituents. It was shown previously that the I86A mutant SADH reduces acetophenone, which is not a substrate of wild-type SADH, to give the anti-Prelog R-product (Musa, M. M.; Lott, N.; Laivenieks, M.; Watanabe, L.; Vieille, C.; Phillips, R. S. ChemCatChem 2009, 1, 89–93.). However, I86A SADH did not reduce aryl ketones with substituents larger than fluorine. We have now expanded the small pocket of the active site of I86A SADH by mutation of Cys-295 to alanine to allow reaction of substituted acetophenones. As predicted, the double mutant I86A/C295A SADH has broadened substrate specificity for meta-substituted, but not para-substituted, acetophenones. However, the increase of the substrate specificity of I86A/C295A SADH is accompanied by a decrease in the k cat /K m values of acetophenones, possibly due to the substrates fitting loosely inside the more open active site. Nevertheless, I86A/C295A SADH gives high conversions and very high enantiomeric excess of the anti-Prelog R-alcohols from the tested substrates.
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      PubDate: 2016-08-12T14:46:11Z
  • Abnormal movement of tropomyosin and response of myosin heads and actin
           during the ATPase cycle caused by the Arg167His, Arg167Gly and Lys168Glu
           mutations in TPM1 gene
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Yurii S. Borovikov, Nikita A. Rysev, Aleksey A. Chernev, Stanislava V. Avrova, Olga E. Karpicheva, Danuta Borys, Małgorzata Śliwińska, Joanna Moraczewska
      Amino acid substitutions: Arg167His, Arg167Gly and Lys168Glu, located in a consensus actin-binding site of the striated muscle tropomyosin Tpm1.1 (TM), were used to investigate mechanisms of the thin filament regulation. The azimuthal movement of TM strands on the actin filament and the responses of the myosin heads and actin subunits during the ATPase cycle were studied using fluorescence polarization of muscle fibres. The recombinant wild-type and mutant TMs labelled with 5-IAF, 1,5-IAEDANS-labelled S1and FITC-phalloidin F-actin were incorporated into the ghost muscle fibres to acquire information on the orientation of the probes relative to the fibre axis. The substitutions Arg167Gly and Lys168Glu shifted TM strands into the actin filament centre, whereas Arg167His moved TM towards the periphery of the filament. In the presence of Arg167Gly-TM and Lys168Glu-TM the fraction of actin monomers that were switched on and the number of the myosin heads strongly bound to F-actin were abnormally high even under conditions close to relaxation. In contrast, Arg167His-TM decreased the fraction of switched on actin and reduced the formation of strongly bound myosin heads throughout the ATPase cycle. We concluded that the altered TM-actin contacts destabilized the thin filament and affected the actin-myosin interactions.
      Graphical abstract image

      PubDate: 2016-08-12T14:46:11Z
  • Glycan structure of Gc Protein-derived Macrophage Activating Factor as
           revealed by mass spectrometry
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Chad R. Borges, Douglas S. Rehder
      Disagreement exists regarding the O-glycan structure attached to human vitamin D binding protein (DBP). Previously reported evidence indicated that the O-glycan of the Gc1S allele product is the linear core 1 NeuNAc-Gal-GalNAc-Thr trisaccharide. Here, glycan structural evidence is provided from glycan linkage analysis and over 30 serial glycosidase-digestion experiments which were followed by analysis of the intact protein by electrospray ionization mass spectrometry (ESI-MS). Results demonstrate that the O-glycan from the Gc1F protein is the same linear trisaccharide found on the Gc1S protein and that the hexose residue is galactose. In addition, the putative anti-cancer derivative of DBP known as Gc Protein-derived Macrophage Activating Factor (GcMAF, which is formed by the combined action of β-galactosidase and neuraminidase upon DBP) was analyzed intact by ESI-MS, revealing that the activating E. coli β-galactosidase cleaves nothing from the protein—leaving the glycan structure of active GcMAF as a Gal-GalNAc-Thr disaccharide, regardless of the order in which β-galactosidase and neuraminidase are applied. Moreover, glycosidase digestion results show that α-N-Acetylgalactosamindase (nagalase) lacks endoglycosidic function and only cleaves the DBP O-glycan once it has been trimmed down to a GalNAc-Thr monosaccharide—precluding the possibility of this enzyme removing the O-glycan trisaccharide from cancer-patient DBP in vivo.
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      PubDate: 2016-08-12T14:46:11Z
  • Processing of A-form ssDNA by cryptic RNase H fold exonuclease PF2046
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Junsoo Kim, Gerelt-Od Sambalkhundev, Sulhee Kim, Jonghyeon Son, Ah-reum Han, Sul-Min Ko, Kwang Yeon Hwang, Woo Cheol Lee
      RNase H fold protein PF2046 of Pyrococcus furiosus is a 3′-5′ ssDNA exonuclease that cleaves after the second nucleotide from the 3′ end of ssDNA and prefers poly-dT over poly-dA as a substrate. In our crystal structure of PF2046 complexed with an oligonucleotide of four thymidine nucleotides (dT4), PF2046 accommodates dT4 tightly in a groove and imposes steric hindrance on dT4 mainly by Phe220 such that dT4 assumes the A-form. As poly-dA prefer B-form due to the stereochemical restrictions, the A-form ssDNA binding by PF2046 should disfavor the processing of poly-dA. Phe220 variants display reduced activity toward poly-dA and the A-form appears to be a prerequisite for the processing by PF2046.

      PubDate: 2016-08-07T14:22:15Z
  • Heat- and pH-induced BSA conformational changes, hydrogel formation and
           application as 3D cell scaffold
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Giovanna Navarra, Chiara Peres, Marco Contardi, Pasquale Picone, Pier Luigi San Biagio, Marta Di Carlo, Daniela Giacomazza, Valeria Militello
      Aggregation and gelation of globular proteins can be an advantage to generate new forms of nanoscale biomaterials based on the fibrillar architecture. Here, we report results obtained by exploiting the proteins' natural tendency to self-organize in 3D network, for the production of new material based on BSA for medical application. In particular, at five different pH values the conformational and structural changes of the BSA during all the steps of the thermal aggregation and gelation have been analyzed by FTIR spectroscopy. The macroscopic mechanical properties of these hydrogels have been obtained by rheological measurements. The microscopic structure of the gels have been studied by AFM and SEM images to have a picture of their different spatial arrangement. Finally, the use of the BSA hydrogels as scaffold has been tested in two different cell cultures.
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      PubDate: 2016-08-07T14:22:15Z
  • Role of active site loop in coenzyme binding and flavin reduction in
           cytochrome P450 reductase
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Robert G. Mothersole, Carla E. Meints, Alex Louder, Kirsten R. Wolthers
      Cytochrome P450 reductase (CPR) contains a loop within the active site (comprising Asp634, Ala635, Arg636 and Asn637; human CPR numbering) that relocates upon NADPH binding. Repositioning of the loop triggers the reorientation of an FAD-shielding tryptophan (Trp679) to a partially stacked conformer, reducing the energy barrier for displacement of the residue by the NADPH nicotinamide ring: an essential step for hydride transfer. We used site-directed mutagenesis and kinetic analysis to investigate if the amino acid composition of the loop influences the catalytic properties of CPR. The D634A and D634N variants elicited a modest increase in coenzyme binding affinity coupled with a 36- and 10-fold reduction in cytochrome c 3+ turnover and a 17- and 3-fold decrease in the pre-steady state rate of flavin reduction. These results, in combination with a reduction in the kinetic isotope effect for hydride transfer, suggest that diminished activity is due to destabilization of the partially stacked conformer of Trp677 and slower release of NADP+. In contrast, R636A, R636S and an A635G/R636S double mutant led to a modest increase in cytochrome c 3+ reduction, which is linked to weaker coenzyme binding and faster interflavin electron transfer. A potential mechanism by which Arg636 influences catalysis is discussed.
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      PubDate: 2016-08-03T14:08:43Z
  • Histone deacetylase inhibitors stimulate the susceptibility of A549 cells
           to a plasma-activated medium treatment
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Tetsuo Adachi, Ayame Kano, Saho Nonomura, Tetsuro Kamiya, Hirokazu Hara
      The number of potential applications of non-thermal atmospheric pressure plasma (NTAPP) discharges in medicine, particularly in cancer therapy, has increased in recent years. NTAPP has been shown to affect cells not only by direct irradiation, but also by an indirect treatment with previously prepared plasma-activated medium (PAM). Histone deacetylase (HDAC) inhibitors have the potential to enhance susceptibility to anticancer drugs and radiation. The aim of the present study was to demonstrate the advantage of the combined application of PAM and HDAC inhibitors on A549 cancer cell survival and elucidate the underlying mechanisms. Cell death with DNA breaks in the nucleus was greater using combined regimens of PAM and HDAC inhibitors such as trichostatin A (TSA) and valproic acid (VPA) than a single PAM treatment and was accompanied by the activation of poly (ADP-ribose) polymerase-1 (PARP-1), depletion of ATP, and elevations in intracellular calcium levels. Moreover, the expression of Rad 51, a DNA repair factor in homologous recombination pathways, was significantly suppressed by the treatment with HDAC inhibitors. These results demonstrate that HDAC inhibitors may synergistically induce the sensitivity of cancer cells to PAM components.
      Graphical abstract image

      PubDate: 2016-08-03T14:08:43Z
  • Decreased expression of the vitamin D receptor in women with recurrent
           pregnancy loss
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Xiaoting Yan, Liqin Wang, Chunfang Yan, Xinwen Zhang, Lingyun Hui, Qiu Sheng, Mingzhan Xue, Xuewen Yu
      The multiple functions of vitamin D3 have stimulated interest in the role that this vitamin may play during pregnancy. The present study investigated the expression of the vitamin D receptor (VDR) in women during the first trimester of pregnancy in order to determine whether VDR is associated with recurrent pregnancy loss (RPL). Forty women at 7–10 weeks gestation with RPL and 40 women of similar gestational age with a healthy pregnancy were recruited. VDR mRNA and protein in chorionic villi and decidua were evaluated by immunohistochemistry, confocal laser scanning microscopy (CLSM), western blot, and quantitative real-time polymerase chain reaction. The serum levels of VDR were measured by an enzyme-linked immunosorbent assay. Women with RPL had a significantly weaker expression of VDR mRNA in villi and decidual tissues compared with the control women (both p < 0.0001). Western blot analysis showed an approximately 46% decrease in VDR expression in villi and a 52% decrease in decidua in the RPL vs. the controls. Serum VDR levels were also significantly lower in the RPL group than in the control group (p = 0.003). Compared with the controls, immunohistochemical and CLSM analysis revealed significantly lower VDR expression in villous cytotrophoblasts and stromal cells, as well as in decidual glandular epithelial and stromal cells (all p < 0.05). In conclusion, these observations show that women with RPL have lower levels of VDR expression in chorionic villi, decidua and serum compared with normal pregnant women, suggesting that decreased VDR expression in the first trimester pregnancy may be associated with RPL.

      PubDate: 2016-08-03T14:08:43Z
  • Low-temperature plasma in biology and medicine
    • Abstract: Publication date: 1 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 605
      Author(s): Masaru Hori, Eun Ha Choi, Shinya Toyokuni

      PubDate: 2016-07-29T13:59:00Z
  • Low-temperature atmospheric-pressure plasma sources for plasma medicine
    • Abstract: Publication date: 1 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 605
      Author(s): Yuichi Setsuhara
      In this review paper, fundamental overviews of low-temperature atmospheric-pressure plasma generation are provided and various sources for plasma medicine are described in terms of operating conditions and plasma properties.

      PubDate: 2016-07-29T13:59:00Z
  • Plasma-on-chip device for stable irradiation of cells cultured in media
           with a low-temperature atmospheric pressure plasma
    • Abstract: Publication date: 1 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 605
      Author(s): Tomohiro Okada, Chun-Yao Chang, Mime Kobayashi, Tetsuji Shimizu, Minoru Sasaki, Shinya Kumagai
      We have developed a micro electromechanical systems (MEMS) device which enables plasma treatment for cells cultured in media. The device, referred to as the plasma-on-chip, comprises microwells and microplasma sources fabricated together in a single chip. The microwells have through-holes between the microwells and microplasma sources. Each microplasma source is located on the backside of each microwells. The reactive components generated by the microplasma sources pass through the through-holes and reach cells cultured in the microwells. In this study, a plasma-on-chip device was modified for a stable plasma treatment. The use of a dielectric barrier discharge (DBD) technique allowed a stable plasma treatment up to 3 min. The plasma-on-chip with the original electrode configuration typically had the maximum stable operation time of around 1 min. Spectral analysis of the plasma identified reactive species such as O and OH radicals that can affect the activity of cells. Plasma treatment was successfully performed on yeast (Saccharomyces cerevisiae) and green algae (Chlorella) cells. While no apparent change was observed with yeast, the treatment degraded the activity of the Chlorella cells and decreased their fluorescence. The device has the potential to help understand interactions between plasma and cells.
      Graphical abstract image

      PubDate: 2016-07-29T13:59:00Z
  • Comparison of free radicals formation induced by cold atmospheric plasma,
           ultrasound, and ionizing radiation
    • Abstract: Publication date: 1 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 605
      Author(s): Mati Ur Rehman, Paras Jawaid, Hidefumi Uchiyama, Takashi Kondo
      Plasma medicine is increasingly recognized interdisciplinary field combining engineering, physics, biochemistry and life sciences. Plasma is classified into two categories based on the temperature applied, namely “thermal” and “non-thermal” (i.e., cold atmospheric plasma). Non-thermal or cold atmospheric plasma (CAP) is produced by applying high voltage electric field at low pressures and power. The chemical effects of cold atmospheric plasma in aqueous solution are attributed to high voltage discharge and gas flow, which is transported rapidly on the liquid surface. The argon-cold atmospheric plasma (Ar-CAP) induces efficient reactive oxygen species (ROS) in aqueous solutions without thermal decomposition. Their formation has been confirmed by electron paramagnetic resonance (EPR) spin trapping, which is reviewed here. The similarities and differences between the plasma chemistry, sonochemistry, and radiation chemistry are explained. Further, the evidence for free radical formation in the liquid phase and their role in the biological effects induced by cold atmospheric plasma, ultrasound and ionizing radiation are discussed.

      PubDate: 2016-07-29T13:59:00Z
  • Nanopore formation process in artificial cell membrane induced by
           plasma-generated reactive oxygen species
    • Abstract: Publication date: 1 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 605
      Author(s): Ryugo Tero, Ryuma Yamashita, Hiroshi Hashizume, Yoshiyuki Suda, Hirofumi Takikawa, Masaru Hori, Masafumi Ito
      We investigated morphological change of an artificial lipid bilayer membrane induced by oxygen radicals which were generated by non-equilibrium atmospheric pressure plasma. Neutral oxygen species, O(3Pj) and O2(1Δg), were irradiated of a supported lipid bilayer existing under a buffer solution at various conditions of dose time and distances, at which the dose amounts of the oxygen species were calculated quantitatively. Observation using an atomic force microscope and a fluorescence microscope revealed that dose of the neutral oxygen species generated nanopores with the diameter of 10–50 nm in a phospholipid bilayer, and finally destructed the bilayer structure. We found that protrusions appeared on the lipid bilayer surface prior to the formation of nanopores, and we attributed the protrusions to the precursor of the nanopores. We propose a mechanism of the pore formation induced by lipid oxidation on the basis of previous experimental and theoretical studies.
      Graphical abstract image

      PubDate: 2016-07-29T13:59:00Z
  • Helicobacter pylori-induced chronic inflammation causes telomere
           shortening of gastric mucosa by promoting PARP-1-mediated non-homologous
           end joining of DNA
    • Abstract: Publication date: Available online 19 July 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Wei-Ping Lee, Ming-Chih Hou, Keng-Hsin Lan, Chung-Pin Li, Yee Chao, Han-Chieh Lin, Shou-Dong Lee
      Helicobacter pylori infection leads to chronic gastritis and increased risk of gastric cancer. The mechanism involves chronic inflammation. We aimed to determine the mechanism by which H. pylori infection causes telomere shortening in inflammatory gastric mucosa. Gastric biopsy specimens were obtained from 20 patients with chronic gastritis or peptic ulcer caused by H. pylori infection. The specimens showed increased NF-κB and superoxide dismutase activities and elevated expressions of PARP-1 and γ-H2AX, all of which returned to normal levels after anti-H. pylori treatment, suggesting that oxidative DNA damage and PARP-1 overexpression might cause telomere shortening. In this report, we adopted DNA end joining assay and showed that H. pylori-infected gastric mucosa had increased alternative NHEJ (non-homologous end joining), implicating that telomere shortening was caused by inflammation-mediated overproduction of reactive oxygen species and PARP-1, leading to telomere shortening.

      PubDate: 2016-07-24T22:49:38Z
  • Interaction of lafutidine in binding to human serum albumin in gastric
           ulcer therapy: STD-NMR, WaterLOGSY-NMR, NMR relaxation times, Tr-NOESY,
           molecule docking, and spectroscopic studies
    • Abstract: Publication date: Available online 22 July 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hongqin Yang, Yanmei Huang, Jiawei He, Shanshan Li, Bin Tang, Hui Li
      In this study, lafutidine (LAF) was used as a model compound to investigate the binding mechanism between antiulcer drugs and human serum albumin (HSA) through various techniques, including STD-NMR, WaterLOGSY-NMR, 1H NMR relaxation times, tr-NOESY, molecule docking calculation, FT-IR spectroscopy, and CD spectroscopy. The analyses of STD-NMR, which derived relative STD (%) intensities, and WaterLOGSY-NMR, determined that LAF bound to HSA. In particular, the pyridyl group of LAF was in close contact with HSA binding pocket, whereas furyl group had a secondary binding. Competitive STD-NMR and WaterLOGSY-NMR experiments, with warifarin and ibuprofen as site-selective probes, indicated that LAF preferentially bound to site II in the hydrophobic subdomains IIIA of HSA. The bound conformation of LAF at the HSA binding site was further elucidated by transferred NOE effect (tr-NOESY) experiment. Relaxation experiments provided quantitative information about the relationship between the affinity and structure of LAF. The molecule docking simulations conducted with AutoDock and the restraints derived from STD results led to three-dimensional models that were consistent with the NMR spectroscopic data. The presence of hydrophobic forces and hydrogen interactions was also determined. Additionally, FT-IR and CD spectroscopies showed that LAF induced secondary structure changes of HSA.
      Graphical abstract image

      PubDate: 2016-07-24T22:49:38Z
  • Effects of macromolecular crowding on a small lipid binding protein probed
           at the single-amino acid level
    • Abstract: Publication date: Available online 22 July 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Silvia Pérez Santero, Filippo Favretto, Serena Zanzoni, Roberto Chignola, Michael Assfalg, Mariapina D'Onofrio
      Macromolecular crowding is a distinctive feature of the cellular interior, influencing the behaviour of biomacromolecules. Despite significant advancements in the description of the effects of crowding on global protein properties, the influence of cellular components on local protein attributes has received limited attention. Here, we describe a residue-level systematic interrogation of the structural, dynamic, and binding properties of the liver fatty acid binding protein (LFABP) in crowded solutions. Two-dimensional NMR spectral fingerprints and relaxation data were collected on LFABP in the presence of polymeric and biomolecular crowders. Non-interacting crowders produced minimal site-specific spectral perturbations on ligand-free and lipid-bound LFABP. Conformational adaptations upon ligand binding reproduced those observed in dilute solution, but a perturbation of the free oleate state resulted in less favorable uptake. When LFABP engaged in direct interactions with background molecules, changes in local chemical environments were detected for residues of the internal binding pocket and of the external surface. Enhanced complexity was introduced by investigating LFABP in cell lysates, and in membrane-bounded compartments. LFABP was able to capture ligands from prokaryotic and eukaryotic cell lysates, and from artificial cells (water-in-oil emulsion droplets). The data suggest that promiscuous interactions are a major factor influencing protein function in the cell.
      Graphical abstract image

      PubDate: 2016-07-24T22:49:38Z
  • Putative binding mode of Escherichia coli exopolyphosphatase and
           polyphosphates based on a hybrid in silico/biochemical approach
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Cristhian Boetsch, Daniel R. Aguayo-Villegas, Fernando D. Gonzalez-Nilo, Á. Teresita Lisa, Paola R. Beassoni
      The exopolyphosphatase of Escherichia coli processively and completely hydrolyses long polyphosphate chains to ortho-phosphate. Genetic surveys, based on the analysis of single ppx − or ppk − mutants and on the double mutant, demonstrate a relationship between these genes and the survival capacity. The exopolyphosphatase belongs to the ASKHA protein superfamily, hence, its active site is well known; however, the knowledge of the way in which this enzyme binds polyP remains incomplete. Here we present different computational approaches, site-direct mutagenesis and kinetic data to understand the relationship between structure and function of exopolyphosphatase. We propose H378 as a fundamental gatekeeper for the recognition of long chain polyphosphate.
      Graphical abstract image

      PubDate: 2016-07-24T22:49:38Z
  • Assessment of plasma acylcarnitines before and after weight loss in obese
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Marieke G. Schooneman, Antonella Napolitano, Sander M. Houten, Graeme K. Ambler, Peter R. Murgatroyd, Sam R. Miller, Carla E.M. Hollak, Chong Y. Tan, Samuel Virtue, Antonio Vidal-Puig, Derek J. Nunez, Maarten R. Soeters
      Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associated with clinical parameters related to glucose metabolism, such as fasting glucose levels and HbA1c. We hypothesized that plasma acylcarnitines would correlate with energy expenditure, insulin sensitivity and other clinical parameters before and during a weight loss intervention. We measured plasma acylcarnitines in 60 obese subjects before and after a 12 week weight loss intervention. These samples originated from three different interventions (diet alone (n = 20); diet and exercise (n = 21); diet and drug treatment (n = 19)). Acylcarnitine profiles were analysed in relation to clinical parameters of glucose metabolism, insulin sensitivity and energy expenditure. Conclusions were drawn from all 60 subjects together. Despite amelioration of HOMA-IR, plasma acylcarnitines levels increased during weight loss. HOMA-IR, energy expenditure and respiratory exchange ratio were not related to plasma acylcarnitines. However non-esterified fatty acids correlated strongly with several acylcarnitines at baseline and during the weight loss intervention (p < 0.001). Acylcarnitines did not correlate with clinical parameters of glucose metabolism during weight loss, questioning their role in insulin resistance and type 2 diabetes mellitus.

      PubDate: 2016-07-24T22:49:38Z
  • Inhibition of precancerous lesions development in kidneys by chrysin via
           regulating hyperproliferation, inflammation and apoptosis at pre clinical
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Summya Rashid, Sana Nafees, Abul Vafa, Shekh Muhammad Afzal, Nemat Ali, Muneeb U. Rehman, Syed Kazim Hasan, Aisha Siddiqi, Preeti Barnwal, Ferial Majed, Sarwat Sultana
      Chrysin (CH) is natural, biologically active compound, belongs to flavoniod family and possesses diverse pharmacological activities as anti-inflammatory, anti-oxidant and anti-cancer. It is found in many plants, honey and propolis. In the present study, we investigated the chemopreventive efficacy of CH against N-nitrosodiethylamine (DEN) initiated and Fe-NTA induced precancerous lesions and its role in regulating oxidative injury, hyperproliferation, tumor incidences, histopathological alterations, inflammation, and apoptosis in the kidneys of Wistar rats. Renal cancer was initiated by single intraperitoneal (i.p.) injection of DEN (200 mg/kg bw) and promoted by twice weekly injection of ferric nitrilotriacetate (Fe-NTA) 9 mg Fe/kg bw for 16 weeks. CH attenuated Fe-NTA enhanced renal lipid peroxidation, serum toxicity markers and restored renal anti oxidant armory significantly. CH supplementation suppressed the development of precancerous lesions via down regulation of cell proliferation marker like PCNA; inflammatory mediators like TNF-α, IL-6, NFkB, COX-2, iNOS; tumor incidences. CH up regulated intrinsic apoptotic pathway proteins like bax, caspase-9 and caspase-3 along with down regulation of Bcl-2 triggering apoptosis. Histopathological and ultra structural alterations further confirmed biochemical and immunohistochemical results. These results provide powerful evidence for the chemopreventive efficacy of CH against chemically induced renal carcinogenesis possibly by modulation of multiple molecular pathways.
      Graphical abstract image

      PubDate: 2016-07-24T22:49:38Z
  • Protein complex formation and intranuclear dynamics of NAC1 in cancer
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Naomi Nakayama, Hiroaki Kato, Gyosuke Sakashita, Yuko Nariai, Kentaro Nakayama, Satoru Kyo, Takeshi Urano
      Nucleus accumbens-associated protein 1 (NAC1) is a cancer-related transcription regulator protein that is also involved in the pluripotency and differentiation of embryonic stem cells. NAC1 is overexpressed in various carcinomas including ovarian, cervical, breast, and pancreatic carcinomas. NAC1 knock-down was previously shown to result in the apoptosis of ovarian cancer cell lines and to rescue their sensitivity to chemotherapy, suggesting that NAC1 may be a potential therapeutic target, but protein complex formation and the dynamics of intranuclear NAC1 in cancer cells remain poorly understood. In this study, analysis of HeLa cell lysates by fast protein liquid chromatography (FPLC) on a sizing column showed that the NAC1 peak corresponded to an apparent molecular mass of 300–500 kDa, which is larger than the estimated molecular mass (58 kDa) of the protein. Furthermore, live cell photobleaching analyses with green fluorescent protein (GFP)-fused NAC1 proteins revealed the intranuclear dynamics of NAC1. Collectively our results demonstrate that NAC1 forms a protein complex to function as a transcriptional regulator in cancer cells.

      PubDate: 2016-07-24T22:49:38Z
  • Analysis of the pH-dependent thermodynamic stability, local motions, and
           microsecond folding kinetics of carbonmonoxycytochrome c
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Rajesh Kumar
      This paper analyzes the effect of pH on thermodynamic stability, low-frequency local motions and microsecond folding kinetics of carbonmonoxycytochrome c (Cyt-CO) all across the alkaline pH-unfolding transition of protein. Thermodynamic analysis of urea-induced unfolding transitions of Cyt-CO measured between pH 6 and pH 11.9 reveals that Cyt-CO is maximally stable at pH∼9.5. Dilution of unfolded Cyt-CO into refolding medium forms a native-like compact state (NCO-state), where Fe2+−CO interaction persists. Kinetic and thermodynamic parameters measured for slow thermally-driven CO dissociation (NCO→N+CO) and association (N+CO→NCO) reactions between pH 6.5 and pH 13 reveal that the thermal-motions of M80-containing Ω-loop are decreased in subdenaturing limit of alkaline pH. Laser photolysis of Fe2+-CO bond in NCO-state triggers the microsecond folding (NCO→N). The microsecond kinetics measured all across the alkaline pH-unfolding transition of Cyt-CO produce rate rollover in the refolding limb of chevron plot, which suggests a glass transition of NCO en route to N. Between pH 7 and pH 11.9, the natural logarithm of the microsecond folding rate varies by < 1.5 units while the natural logarithm of apparent equilibrium constant varies by 11.8 units. This finding indicates that the pH-dependent ionic-interactions greatly affect the global stability of protein but have very small effect on folding kinetics.
      Graphical abstract image

      PubDate: 2016-07-24T22:49:38Z
  • Chronic intermittent hypoxia induces cardiac hypertrophy by impairing
           autophagy through the adenosine 5′-monophosphate-activated protein
           kinase pathway
    • Abstract: Publication date: 15 September 2016
      Source:Archives of Biochemistry and Biophysics, Volume 606
      Author(s): Sheng Xie, Yan Deng, Yue-ying Pan, Jie Ren, Meng Jin, Yu Wang, Zhi-hua Wang, Die Zhu, Xue-ling Guo, Xiao Yuan, Jin Shang, Hui-guo Liu
      Autophagy is tightly regulated to maintain cardiac homeostasis. Impaired autophagy is closely associated with pathological cardiac hypertrophy. However, the relationship between autophagy and cardiac hypertrophy induced by chronic intermittent hypoxia (CIH) is not known. In the present study, we measured autophagy-related genes and autophagosomes during 10 weeks of CIH in rats, and 6 days in H9C2 cardiomyocytes, and showed that autophagy was impaired. This conclusion was confirmed by the autophagy flux assay. We detected significant hypertrophic changes in myocardium with impaired autophagy. Rapamycin, an autophagy enhancer, attenuated the cardiac hypertrophy induced by CIH. Moreover, silencing autophagy-related gene 5 (ATG5) exerted the opposite effect. The role of adenosine monophosphate-activated protein kinase (AMPK) in regulating autophagy under CIH was confirmed using AICAR to upregulate this enzyme and restore autophagy flux. Restoring autophagy by AICAR or rapamycin significantly reversed the hypertrophic changes in cardiomyocytes. To investigate the mechanism of autophagy impairment, we compared phospho (p)-AMPK, p-Akt, cathepsin D, and NFAT3 levels, along with calcineurin activity, between sham and CIH groups. CIH activated calcineurin, and inhibited AMPK and AMPK-mediated autophagy in an Akt- and NFAT3-independent manner. Collectively, these data demonstrated that impaired autophagy induced by CIH through the AMPK pathway contributed to cardiac hypertrophy.

      PubDate: 2016-07-24T22:49:38Z
  • Gypsy moth pheromone-binding protein-ligand interactions: pH profiles and
           simulations as tools for detecting polar interactions
    • Abstract: Publication date: Available online 16 July 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jurgen T. Sanes, Erika Plettner
      Pheromone-binding proteins (PBPs) are believed to control diffusion of pheromones in sensory hairs of insects. The interactions of gypsy moth (Lymantria dispar) PBPs with the sex attractant pheromone, (+)-Disparlure ((7R,8S)-epoxy-2-methyloctadecane), and the enantioselectivity of recognition are not completely understood. Enantioselectivity is important for L. dispar, because (-)-disparlure cancels the attraction of (+)-disparlure, so these moths use enantiopure (+)-disparlure for communication. We performed docking simulations of the protonated homology PBP models with the enantiomers of disparlure, 5-oxadisparlure, 10-oxadisparlure, 5-thiadisparlure and 10-thiadisparlure, together with a binding assay experiment, in which the pH profiles for the PBP-ligand combinations were surveyed. The molecular simulations revealed different amino acid residues in the binding sites, movement of specific amino acid residues at certain pH values, distinct amino acid-ligand interactions (side chain donors/acceptors, H-arene bonding, backbone donors/acceptors) and differences in the conformations of each protein-ligand complex. The pK a values obtained from the binding experiment and the results from the molecular simulations served as tools for detecting polar interactions between the PBPs and ligands. The differences found between structures docked with ligand enantiomers reveal the enantioselectivity of the gypsy moth PBPs towards the pheromone and its antipode, as well as towards enantiomers of pheromone analogs with heteroatom substitutions.

      PubDate: 2016-07-19T22:42:45Z
  • Human topoisomerase IB is a target of a thiosemicarbazone copper(II)
    • Abstract: Publication date: Available online 16 July 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Venn Vutey, Silvia Castell i, Ilda D'Annessa, Luciana B.P. Sâmia, Elaine M. Souza-Fagundes, Heloisa Beraldo, Alessandro Desideri
      The human topoisomerase IB inhibition and the antiproliferative activity of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone HPyCT4BrPh alone and its copper(II) complex [Cu(PyCT4BrPh)Cl] was investigated. [Cu(PyCT4BrPh)Cl] inhibits both the DNA cleavage and religation step of the enzyme, whilst the ligand alone does not display any effect. In addition we show that coordination to copper(II) improves the cytotoxicity of HPyCT4BrPh against THP-1 leukemia and MCF-7 breast cancer cells. The data indicate that the copper(II) thiosemicarbazone complex may hit human topoisomerase IB and that metal coordination can be useful to improve cytotoxicity of this versatile class of compounds.
      Graphical abstract image

      PubDate: 2016-07-19T22:42:45Z
  • Phospho-transfer networks and ATP homeostasis in response to an
           ineffective electron transport chain in Pseudomonas fluorescens
    • Abstract: Publication date: Available online 16 July 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): V.P. Appanna, A.A. Alhasawi, C. Auger, S.C. Thomas, V.D. Appanna
      Although oxidative stress is known to impede the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, the nutritionally-versatile microbe, Pseudomonas fluorescens has been shown to proliferate in the presence of hydrogen peroxide (H2O2) and nitrosative stress. In this study we demonstrate the phospho-transfer system that enables this organism to generate ATP was similar irrespective of the carbon source utilized. Despite the diminished activities of enzymes involved in the TCA cycle and in the electron transport chain (ETC), the ATP levels did not appear to be significantly affected in the stressed cells. Phospho-transfer networks mediated by acetate kinase (ACK), adenylate kinase (AK), and nucleoside diphosphate kinase (NDPK) are involved in maintaining ATP homeostasis in the oxidatively-challenged cells. This phospho-relay machinery orchestrated by substrate-level phosphorylation is aided by the up-regulation in the activities of such enzymes like phosphoenolpyruvate carboxylase (PEPC), pyruvate orthophosphate dikinase (PPDK), and phosphoenolpyruvate synthase (PEPS). The enhanced production of phosphoenolpyruvate (PEP) and pyruvate further fuel the synthesis of ATP. Taken together, this metabolic reconfiguration enables the organism to fulfill its ATP need in an O2-independent manner by utilizing an intricate phospho-wire module aimed at maximizing the energy potential of PEP with the participation of AMP.
      Graphical abstract image

      PubDate: 2016-07-19T22:42:45Z
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