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  Subjects -> BIOLOGY (Total: 2916 journals)
    - BIOCHEMISTRY (219 journals)
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BIOCHEMISTRY (219 journals)                  1 2     

Showing 1 - 0 of 0 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 4)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Central Science     Hybrid Journal   (Followers: 2)
ACS Chemical Biology     Full-text available via subscription   (Followers: 142)
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: 12)
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: 5)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 69)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 12)
American Journal of Polymer Science     Open Access   (Followers: 20)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical Biochemistry     Hybrid Journal   (Followers: 137)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 49)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 8)
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: 21)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (Followers: 1)
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Asian Journal of Biomedical and Pharmaceutical Sciences     Open Access   (Followers: 2)
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: 18)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 4)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 12)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 27)
Biochemical Pharmacology     Hybrid Journal   (Followers: 8)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 3)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 195)
Biochemistry & Pharmacology : Open Access     Open Access   (Followers: 1)
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: 4)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 7)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 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: 10)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 27)
Biomaterials Research     Open Access   (Followers: 2)
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: 45)
Bit├ícora Digital     Open Access  
BMC Biochemistry     Open Access   (Followers: 12)
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)
Central European Journal of Chemistry     Hybrid Journal   (Followers: 6)
ChemBioChem     Hybrid Journal   (Followers: 6)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 22)
Chemical Engineering Journal     Hybrid Journal   (Followers: 21)
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: 30)
Chemistry and Ecology     Hybrid Journal  
ChemTexts     Hybrid Journal  
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 19)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 60)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 4)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 1)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 7)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 2)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 10)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 4)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 21)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 5)
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: 3)
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: 7)
Green Chemistry     Full-text available via subscription   (Followers: 9)
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  
Indonesian Biomedical Journal     Open Access  
Insect Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 3)
International Journal of Biochemistry & Cell Biology     Hybrid Journal   (Followers: 6)
International Journal of Biochemistry and Biophysics     Open Access  
International Journal of Biological Chemistry     Open Access   (Followers: 4)
International Journal of Food Contamination     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: 41)
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 161)
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: 3)
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: 5)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Molecular Biochemistry     Open Access   (Followers: 2)
Journal of Neurochemistry     Hybrid Journal   (Followers: 2)
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: 2)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 6)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Marine Chemistry     Hybrid Journal   (Followers: 6)
Molecular and Biochemical Parasitology     Hybrid Journal   (Followers: 2)
Molecular and Cellular Biochemistry     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 4)
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: 67)
Nature Communications     Open Access   (Followers: 97)
Novelty in Biomedicine     Open Access  
Ocean Acidification     Open Access   (Followers: 1)
Organic & Biomolecular Chemistry     Full-text available via subscription   (Followers: 75)
Parasitology Open     Open Access  
Peptidomics     Open Access  
Pesticide Biochemistry and Physiology     Hybrid Journal   (Followers: 4)
Pharmaceutical Bioprocessing     Full-text available via subscription   (Followers: 1)
Pharmacognosy Magazine     Open Access   (Followers: 2)
Pharmacognosy Research     Open Access   (Followers: 3)
Pharmacognosy Reviews     Open Access   (Followers: 1)
Phytochemistry Reviews     Hybrid Journal  
Plant Physiology and Biochemistry     Hybrid Journal   (Followers: 7)
Plasma Chemistry and Plasma Processing     Hybrid Journal   (Followers: 2)
Polymer Journal     Hybrid Journal   (Followers: 1)
Preparative Biochemistry and Biotechnology     Hybrid Journal   (Followers: 4)
Process Biochemistry     Full-text available via subscription   (Followers: 5)
Processes     Open Access  
Progress in Histochemistry and Cytochemistry     Hybrid Journal   (Followers: 1)

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.602]   [H-I: 124]   [21 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [2970 journals]
  • Switching of actin-myosin motors by voltage-induced pH bias in vitro
    • Abstract: Publication date: Available online 20 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kuniyuki Hatori, Takahiro Iwase, Reito Wada
      ATP-driven motor proteins, which function in cell motility and organelle transport, have potential applications as bio-inspired micro-devices; however, their control remains unsatisfactory. Here, we show rapid-velocity control of actin filaments interacting with myosin motors using voltage applied to Pt electrodes in an in vitro motility system, by which immediate increases and decreases in velocity were induced beside the cathode and anode, respectively. Indicator dye revealed pH changes after voltage application, and alternate voltage switching allowed actin filaments to cyclically alter their velocity in response to these changes. This principle provides a basis for on-demand control of not only motor proteins but also pH-sensitive events at a microscopic level.


      PubDate: 2016-05-24T10:51:59Z
       
  • Nanopore formation process in artificial cell membrane induced by
           plasma-generated reactive oxygen species
    • Abstract: Publication date: Available online 20 May 2016
      Source:Archives of Biochemistry and Biophysics
      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: 2016-05-24T10:51:59Z
       
  • Peroxynitrite-induced structural perturbations in human IgG: A
           physicochemical study
    • Abstract: Publication date: Available online 19 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Mir Yasir Arfat, Zarina Arif, Sumit Kumar Chaturvedi, Moinuddin, Khursheed Alam
      IgG is an important defence protein. To exhibit optimum function the molecule must maintain its native structure. Peroxynitrite is a potent oxidizing and nitrating agent produced in vivo under pathophysiological conditions. It can oxidize and/or nitrate various amino acids causing changes in the structure and function of proteins. Such proteins may be involved in the pathogenesis of many inflammatory diseases, including rheumatoid arthritis. In the present work, peroxynitrite-induced structural changes in IgG have been studied by UV–visible, fluorescence, CD, FT-IR, DLS spectroscopy and DSC as well as by SDS–PAGE. Peroxynitrite-modified IgG exhibited hyperchromicity at 280 nm, quenching of tryptophan fluorescence, increase in ANS fluorescence, loss of β-sheet, shift in the positions of amide I and amide II bands, appearance of new peak in FT-IR, attachment of nitro residues and increase in melting temperature, compared to native IgG. Furthermore, peroxynitrite-modified IgG exhibited an additional peak at 420 nm, quenching in tyrosine fluorescence and enhancement in dityrosine fluorescence compared to native IgG. Generation of nitrotyrosine, dityrosine and nitrotryptophan was also observed in peroxynitrite-modified IgG. Gross structural changes in IgG caused by peroxynitrite and observed in vitro may favour autoantibodies induction in vivo under similar conditions.


      PubDate: 2016-05-24T10:51:59Z
       
  • Cross talk between MMP2-Spm-Cer-S1P and ERK1/2 in proliferation of
           pulmonary artery smooth muscle cells under angiotensin II stimulation
    • Abstract: Publication date: Available online 20 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Animesh Chowdhury, Jaganmay Sarkar, Pijush Kanti Pramanik, Tapati Chakraborti, Sajal Chakraborti
      The aim of the present study is to establish the mechanism associated with the proliferation of PASMCs under ANG II stimulation. The results showed that treatment of PASMCs with ANG II induces an increase in cell proliferation and 100 nM was the optimum concentration for maximum increase in proliferation of the cells. Pretreatment of the cells with AT1, but not AT2 receptor antagonist inhibited ANG II induced cell proliferation. Pretreatment with pharmacological and genetic inhibitors of sphingomyelinase (SMase) and sphingosine kinase (SPHK) prevented ANG II-induced cell proliferation. ANG II has also been shown to induce SMase activity, SPHK phosphorylation and S1P production. In addition, ANG II caused an increase in proMMP-2 expression and activation, ERK1/2 phosphorylation and NADPH oxidase activation. Upon inhibition of MMP-2, SMase activity and S1P level were curbed leading to inhibition of cell proliferation. SPHK was phosphorylated by ERK1/2 during ET-1 stimulation of the cells. ANG II-induced ERK1/2 phosphorylation and proMMP-2 expression and activation in the cells were abrogated upon inhibition of NADPH oxidase activity. Overall, NADPH oxidase plays an important role in proMMP-2 expression and activation and that MMP-2 mediated SMC proliferation occurs through the involvement of Spm-Cer-S1P signaling axis under ANG II stimulation of PASMCs.


      PubDate: 2016-05-24T10:51:59Z
       
  • Preparation of ribosomes for smFRET studies: A simplified approach
    • Abstract: Publication date: Available online 19 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Bassem Shebl, Drew E. Menke, Min Pennella, Raghav R. Poudyal, Donald H. Burke, Peter V. Cornish
      During the past decade, single-molecule studies of the ribosome have significantly advanced our understanding of protein synthesis. The broadest application of these methods has been towards the investigation of ribosome conformational dynamics using single-molecule Förster resonance energy transfer (smFRET). The recent advances in fluorescently labeled ribosomes and translation components have resulted in success of smFRET experiments. Various methods have been employed to target fluorescent dyes to specific locations within the ribosome. Primarily, these methods have involved additional steps including subunit dissociation and/or full reconstitution, which could result in ribosomes of reduced activity and translation efficiency. In addition, substantial time and effort are required to produce limited quantities of material. To enable rapid and large-scale production of highly active, fluorescently labeled ribosomes, we have developed a procedure that combines partial reconstitution with His-tag purification. This allows for a homogeneous single-step purification of mutant ribosomes and subsequent integration of labeled proteins. Ribosomes produced with this method are shown to be as active as ribosomes purified using classical methods. While we have focused on two labeling sites in this report, the method is generalizable and can in principle be extended to any non-essential ribosomal protein.


      PubDate: 2016-05-19T09:52:37Z
       
  • Antiatherogenic effects of ellagic acid and urolithins in vitro
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Laura Mele, Pedro Mena, Antonio Piemontese, Valentina Marino, Noelia López-Gutiérrez, Franco Bernini, Furio Brighenti, Ilaria Zanotti, Daniele Del Rio
      Atherosclerosis, one of the leading causes of death worldwide, is characterized by impaired endothelial function and lipid metabolism, among other factors. Ellagitannins are a class of phenolic compounds that may play a role in cardiovascular health. This work aimed to study the potential atheroprotective effects of urolithins, ellagitannin-derived gut microbiota metabolites, on different key factors in atherosclerosis development: the ability of monocytes to adhere to endothelial cells and the uptake and efflux of cholesterol by macrophages. The biotransformations urolithins undergo in peripheral cells were also evaluated. Results indicated that some urolithins and ellagic acid were able to reduce the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the secretion of a cellular adhesion molecule (sVCAM-1) and pro-inflammatory cytokine (IL-6). Urolithin C, a combination of urolithins A and B, and ellagic acid also decreased the accumulation of cholesterol in THP-1-derived macrophages, but they were not able to promote cholesterol efflux. The analysis of cell media by UHPLC-ESI-MSn indicated urolithins and ellagic underwent extensive metabolism, with sulfate and methyl conjugation. This evidence indicates that atherosclerotic processes may be attenuated by urolithins, but future human intervention trials are required to establish if is translated in vivo.


      PubDate: 2016-05-19T09:52:37Z
       
  • Anthocyanins and their gut metabolites reduce the adhesion of monocyte to
           TNFα-activated endothelial cells at physiologically relevant
           concentrations
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Irena Krga, Laurent-Emmanuel Monfoulet, Aleksandra Konic-Ristic, Sylvie Mercier, Maria Glibetic, Christine Morand, Dragan Milenkovic
      An increasing number of evidence suggests a protective role of dietary anthocyanins against cardiovascular diseases. Anthocyanins' extensive metabolism indicates that their metabolites could be responsible for the protective effects associated with consumption of anthocyanin-rich foods. The aim of this work was to investigate the effect of plasma anthocyanins and their metabolites on the adhesion of monocytes to TNFα-activated endothelial cells and on the expression of genes encoding cell adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were exposed to circulating anthocyanins: cyanidin-3-arabinoside, cyanidin-3-galactoside, cyanidin-3-glucoside, delphinidin-3-glucoside, peonidin-3-glucoside, anthocyanin degradation product: 4-hydroxybenzaldehyde, or to their gut metabolites: protocatechuic, vanillic, ferulic and hippuric acid, at physiologically-relevant concentrations (0.1–2 μM) and time of exposure. Both anthocyanins and gut metabolites decreased the adhesion of monocytes to HUVECs, with a magnitude ranging from 18.1% to 47%. The mixture of anthocyanins and that of gut metabolites also reduced monocyte adhesion. However, no significant effect on the expression of genes encoding E-selectin, ICAM1 and VCAM1 was observed, suggesting that other molecular targets are involved in the observed effect. In conclusion, this study showed the potency of anthocyanins and their gut metabolites to modulate the adhesion of monocytes to endothelial cells, the initial step in atherosclerosis development, under physiologically-relevant conditions.
      Graphical abstract image

      PubDate: 2016-05-19T09:52:37Z
       
  • Xanthohumol improves dysfunctional glucose and lipid metabolism in
           diet-induced obese C57BL/6J mice
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Cristobal L. Miranda, Valerie D. Elias, Joshua J. Hay, Jaewoo Choi, Ralph L. Reed, Jan F. Stevens
      Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice.
      Graphical abstract image

      PubDate: 2016-05-19T09:52:37Z
       
  • Identification and quantification of novel cranberry-derived plasma and
           urinary (poly)phenols
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Rodrigo P. Feliciano, Albert Boeres, Luca Massacessi, Geoffrey Istas, M. Rita Ventura, Cláudia Nunes dos Santos, Christian Heiss, Ana Rodriguez-Mateos
      Cranberries are a rich source of (poly)phenols, in particular proanthocyanidins, anthocyanins, flavonols, and phenolic acids. However, little is known about their bioavailability in humans. We investigated the absorption, metabolism, and excretion of cranberry (poly)phenols in plasma and urine of healthy young men after consumption of a cranberry juice (787 mg (poly)phenols). A total of 60 cranberry-derived phenolic metabolites were identified using UPLC-Q-TOF-MS analysis with authentic standards. These included sulfates of pyrogallol, valerolactone, benzoic acids, phenylacetic acids, glucuronides of flavonols, as well as sulfates and glucuronides of cinnamic acids. The most abundant plasma metabolites were small phenolic compounds, in particular hippuric acid, catechol-O-sulfate, 2,3-dihydroxybenzoic acid, phenylacetic acid, isoferulic acid, 4-methylcatechol-O-sulfate, α-hydroxyhippuric acid, ferulic acid 4-O-sulfate, benzoic acid, 4-hydroxyphenyl acetic acid, dihydrocaffeic acid 3-O-sulfate, and vanillic acid-4-O-sulfate. Some benzoic acids, cinnamic acids, and flavonol metabolites appeared in plasma early, at 1–2 h post-consumption. Others such as phenylacetic acids, benzaldehydes, pyrogallols, catechols, hippuric and dihydrocinnamic acid derivatives appear in plasma later (Tmax 4–22 h). The 24 h urinary recovery with respect to the amount of (poly)phenols consumed was 6.2%. Our extensive description of the bioavailability of cranberry (poly)phenols lays important groundwork necessary to start understanding the fate of these compounds in humans.


      PubDate: 2016-05-19T09:52:37Z
       
  • Special Issue: “Polyphenols and health”
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Christine Morand, Helmut Sies



      PubDate: 2016-05-19T09:52:37Z
       
  • Butyric acid increases transepithelial transport of ferulic acid through
           upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and
           SLC16A3 (MCT4)
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Kerstin Ziegler, Asimina Kerimi, Laure Poquet, Gary Williamson
      Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid.


      PubDate: 2016-05-19T09:52:37Z
       
  • (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice
    • Abstract: Publication date: 1 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 599
      Author(s): Eleonora Cremonini, Ahmed Bettaieb, Fawaz G. Haj, Cesar G. Fraga, Patricia I. Oteiza
      Obesity constitutes a major public health concern, being frequently associated with type 2 diabetes (T2D). Evidence from studies in humans and experimental animals suggest that consumption of the flavan-3-ol (-)-epicatechin (EC) and of EC-rich foods may improve insulin sensitivity. To further understand the potential benefits of dietary EC consumption on insulin resistance, this study investigated the capacity of EC supplementation to prevent high fat diet (HFD)-induced insulin resistance in mice. To assess the underlying mechanisms, the effects of HFD and EC consumption on the activation of the insulin cascade and of its negative modulators were evaluated. HFD consumption for 15 w caused obesity and insulin resistance in C57BL/6J mice as evidenced by high fasted and fed plasma glucose and insulin levels, and impaired ITT and GTT tests. This was associated with alterations in the activation of components of the insulin-triggered signaling cascade (insulin receptor, IRS1, ERK1/2, Akt) in adipose and liver tissues. EC supplementation prevented/ameliorated all these parameters. EC acted improving insulin sensitivity in the HFD-fed mice in part through a downregulation of the inhibitory molecules JNK, IKK, PKC and protein tyrosine phosphatase 1B (PTP1B). Thus, the above results suggest that consumption of EC-rich foods could constitute a dietary strategy to mitigate obesity-associated insulin resistance.
      Graphical abstract image

      PubDate: 2016-05-19T09:52:37Z
       
  • Approaches to the solution of coupled multiexponential transient-state
           rate kinetic equations: A critical review
    • Abstract: Publication date: Available online 9 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Harvey F. Fisher
      The transient-state kinetic approach has failed to reach its full potential despite its advantage over the steady-state approach in its ability to observe mechanistic events directly and in real time. This failure has been due in part to the lack of any rigorously derived and readily applicable body of theory corresponding to that which currently characterizes the steady-state approach. In order to clarify the causes of this discrepancy and to suggest a route to its solution we examine the capabilities and limitations of the various forms of transient-state kinetic approaches to the mathematical resolution of enzymatic reaction mechanisms currently available. We document a lack of validity inherent in their basic assumptions and suggest the need for a potentially more rigorous analytic approach.


      PubDate: 2016-05-14T09:45:05Z
       
  • Identification of the two-phase mechanism of arachidonic acid regulating
           
    • Abstract: Publication date: Available online 10 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hironari Akasaka, Ke-He Ruan
      Through linking inducible cyclooxygenase (COX)-2 with microsomal prostaglandin E2 (PGE2) synthase-1 (mPGES-1), a Single-Chain Enzyme Complex (SCEC, COX-2-10aa-mPGES-1) was engineered to mimic a specific inflammatory PGE2 biosynthesis from omega-6 fatty acid, arachidonic acid (AA), by eliminating involvements of non-inducible COX-1 and other PGE2 synthases. Using the SCEC, we characterized coupling reactions between COX-2 and mPGES-1 at 1:1 ratio of inflammatory PGE2 production. AA demonstrated two phase activities to regulate inflammatory PGE2 production. In the first phase (<2 μM), AA was a COX-2 substrate and converted to increasing production of PGE2. In the second phase with a further increased AA level (2–10 μM), AA bound to mPGES-1 and inhibited the PGE2 production. The SCEC study was identical to the co-expression of COX-2 and mPGES-1. This was further confirmed by using mPGES-1 and PGH2 as a direct enzyme target and substrate, respectively. Furthermore, the carboxylic acid group of AA binding to R67 and R70 of mPGES-1 was identified by X-ray structure-based docking and mutagenesis. mPGES-1 mutants, R70A, R70K, R67A and R67K, lost 40–100% binding to [14C]-AA. To conclude, a cellular model, in which AA is involved in self-controlling initial initiating and later resolving inflammation by its two phase activities, was discussed.


      PubDate: 2016-05-14T09:45:05Z
       
  • Biochemical properties of Glu-SH3 as a family 13 glycoside hydrolase with
           remarkable substrate specificity for trehalose: Implications to
           sequence-based classification of CAZymes
    • Abstract: Publication date: Available online 10 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kamran Khalili Ghadikolaei, Maral Shojaei, Armin Ghaderi, Farzaneh Hojjati, Kambiz Akbari Noghabi, Hossein Shahbani Zahiri
      A novel glycoside hydrolase from Exiguobacterium sp. SH3 was characterized. The enzyme, designated as Glu-SH3, was predicted by in silico analysis to have structural similarity with members of oligo-1,6-glucosidase and trehalose-6-phosphate hydrolase subfamilies in the GH-13 family of glycoside hydrolases. The gene was expressed in E. coli and the recombinant enzyme was purified as a His-tagged protein of about 60 kDa. The enzyme was shown to have remarkable substrate specificity for trehalose. The characteristic ability of Glu-SH3 to hydrolyze trehalose was ascertained by zymography, thin layer chromatography, and NMR spectroscopy. The maximum activity of Glu-SH3 was obtained at 35 °C and pH 7, but it was able to exhibit more than 90% of the activity within the pH range of 5-8. The V max and K m values were estimated to be 170 U and 4.5 mg ml−1, respectively. By comparison with trehalases, Glu-SH3 with K cat and K cat /K m values of 1552 s−1 and 119.4 mM−1 s−1 can be recognized as a very efficient trehalose-hydrolyzing glycosidase. Given the phylogeny and the substrate specificity of Glu-SH3, it may be assumed that the enzyme shares a common ancestor with oligo-1,6-glucosidases but have evolved distinctly to serve a physiological function in trehalose metabolism.


      PubDate: 2016-05-14T09:45:05Z
       
  • Nuclear localization of formyl-peptide receptor 2 in human cancer cells
    • Abstract: Publication date: Available online 10 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Fabio Cattaneo, Melania Parisi, Tiziana Fioretti, Daniela Sarnataro, Gabriella Esposito, Rosario Ammendola
      Current models of G protein-coupled receptors (GPCRs) signaling describe binding of external agonists to cell surface receptors which, in turn, trigger several biological responses. New paradigms indicate that GPCRs localize to and signal at the nucleus, thus regulating distinct signaling cascades. The formyl-peptide receptor FPR2 belongs to the GPCR super-family and is coupled to PTX-sensitive Gi proteins. We show by western blot analysis, immunofluorescence experiments and radioligand binding assays that FPR2 is expressed at nuclear level in CaLu-6 and AGS cells. Nuclear FPR2 is a functional receptor, since it participates in intra-nuclear signaling, as assessed by decreased G protein-FPR2 association and enhanced ERK2, c-Jun and c-Myc phosphorylation upon stimulation of intact nuclei with the FPR2 agonist, WKYMVm. We analyzed FPR2 sequence for the search of a nuclear localization sequence (NLS) and we found a stretch of basic aminoacids (227-KIHKK-231) in the third cytoplasmic loop of the receptor. We performed single (K230A) and multiple (H229A/K230A/K231A) mutagenesis of NLS. The constructs were individually overexpressed in HEK293 cells and immunofluorescence and western blot analysis showed that nuclear localization or translocation of FPR2 depends on the integrity of the H229 and K231 residues within the NLS.


      PubDate: 2016-05-14T09:45:05Z
       
  • Diastolic dysfunction and cardiac troponin I decrease in aging hearts
    • Abstract: Publication date: Available online 13 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): B. Pan, Z.W. Xu, Y. Xu, L.J. Liu, J. Zhu, X. Wang, C. Nan, Z. Zhang, W. Shen, X.P. Huang, J. Tian
      Cardiac tropnoin I (cTnI) plays a critical role in the regulation of diastolic function, and its low expression may result in cardiac diastolic dysfunction, which is the most common form of cardiovascular disorders in older adults. In this study, cTnI expression levels were determined in mice at various ages and cardiac function was measured and compared between young adult mice (3 and 10 months) and older mice (18 months). The data indicated that the cTnI levels reached a peak high in young adult hearts (3 months), but decreased in older hearts (18 months). Furthermore, the older hearts showed a significant diastolic dysfunction observed by P–V loop and echocardiography measurements. To further define the mechanism underlying the cTnI decrease in aging hearts, we tested DNA methylation and histone acetylation modifications of cTnI gene. We found that acetylation of histone near the promoter region of cTnI gene played an important role in regulation of cTnI expression in the heart at different ages. Our study indicates that epigenetic modification caused cTnI expression decrease is one of the possible causes that result in a reduced cTnI level and diastolic dysfunction in the older hearts.


      PubDate: 2016-05-14T09:45:05Z
       
  • Cold-inducible RNA binding protein regulates mucin expression induced by
           cold temperatures in human airway epithelial cells
    • Abstract: Publication date: Available online 13 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): DanHua Ran, LingXiu Chen, WenYao Xie, Qing Xu, Zhong Han, HuaPing Huang, XiangDong Zhou
      Mucus overproduction is an important manifestation of chronic airway inflammatory diseases, however, the mechanisms underlying the association between cold air and mucus overproduction remain unknown. We found that the expression of the cold-inducible RNA binding protein (CIRP) was increased in patients with chronic obstructive pulmonary disease (COPD). In the present study, we tested whether CIRP was involved in inflammatory factors and mucin5AC (MUC5AC) expression after cold stimulation and investigated the potential signaling pathways involved in this process. We found that CIRP was highly expressed in the bronchi of COPD patients. The expression of CIRP, interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were increased, and the CIRP was localized in cytoplasm after cold stimulation. MUC5AC mRNA and protein expression levels were elevated in a temperature- and time-dependent manner after cold stimulation and were associated with the phosphorylation of ERK and NF-κB, which reflected their activation. These responses were suppressed by knockdown of CIRP with a specific siRNA or the ERK and NF-κB inhibitors. These results demonstrated that CIRP was expressed in the bronchi of human COPD patients and was involved in inflammatory factors and MUC5AC expression after cold stimulation through the ERK and NF-κB pathways.


      PubDate: 2016-05-14T09:45:05Z
       
  • Myofilament Modulation of Contraction
    • Abstract: Publication date: Available online 6 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Brandon J. Biesiadecki



      PubDate: 2016-05-09T09:26:32Z
       
  • Macromolecular crystallography: an old science with new perspectives
    • Abstract: Publication date: Available online 6 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ana Camara-Artigas, Jose Antonio Gavira



      PubDate: 2016-05-09T09:26:32Z
       
  • Antibacterial properties and mechanism of graphene oxide-silver
           nanocomposites as bactericidal agents for water disinfection
    • Abstract: Publication date: Available online 8 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Biao Song, Chang Zhang, Guangming Zeng, Jilai Gong, Yingna Chang, Yan Jiang
      Providing clean and affordable drinking water without harmful disinfection byproducts generated by conventional chemical disinfectants gives rise to the need for technological innovation. Nanotechnology has great potential in purifying water and wastewater treatment. A graphene oxide-silver (GO-Ag) nanocomposite with excellent antibacterial activity was prepared and characterized by transmission electron microscope and X-ray photoelectron spectroscopy. The tests were carried out using Escherichia coli and Staphylococcus aureus as model strains of Gram-negative and Gram-positive bacteria, respectively. The effect of bactericide dosage and pH on antibacterial activity of GO-Ag was examined. Morphological observation of bacterial cells by scanning electron microscope showed that GO-Ag was much more destructive to cell membrane of Escherichia coli than that of Staphylococcus aureus. Experiments were carried out using catalase, superoxide dismutase and sodium thioglycollate to investigate the formation of reactive oxygen species and free silver ions in the bactericidal process. The activity of intracellular antioxidant enzymes was measured to investigate the potential role of oxidative stress. According to the consequence, synergetic mechanism including destruction of cell membranes and oxidative stress accounted for the antibacterial activity of GO-Ag nanocomposites. All the results suggested that GO-Ag nanocomposites displayed a good potential for application in water disinfection.
      Graphical abstract image

      PubDate: 2016-05-09T09:26:32Z
       
  • What is the concentration of hydrogen peroxide in blood and plasma'
    • Abstract: Publication date: Available online 9 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Henry Jay Forman, Angelito Bernardo, Kelvin J.A. Davies
      The concentration of hydrogen peroxide (H2O2) in blood and plasma is a measurement that has often been made, but the absolute values remain unsettled due the great variability of results actually published in the literature. As in every tissue, the concentration of H2O2 in blood and plasma is determined by the dynamics of its production versus its removal. The major sources of H2O2 in cells will only be briefly described as they are already well documented, The production of H2O2 in red blood cells will be described as it is less well known. But, the concentration of H2O2 within cells is more problematic. Intracellular H2O2 concentration has been estimated based on the kinetics of production and elimination, while its determination is technically difficult. Furthermore, compartmentalization and gradients result in its quantitation only as an average. The sources of extracellular H2O2, particularly in plasma, will also be described briefly. The major question addressed here however, is the actual concentration of H2O2 in plasma, which has been studied extensively, but still remains controversial.
      Graphical abstract image

      PubDate: 2016-05-09T09:26:32Z
       
  • Aggregation of intrinsically disordered fibrinogen as the influence of
           backbone conformation
    • Abstract: Publication date: Available online 3 May 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Aabgeena Naeem, Sheraz Ahmad Bhat, Afshin Iram, Rizwan Hasan Khan
      Fib having intrinsically disordered αC domains is involved in coagulation cascade and thrombosis. Fib molecules forms prefibrillar oligomers at 30%, and associate in 40% and 50% TFE to proceed α to β transition, suggesting the formation of an intermolecular β-structure. AFM images confirmed the nature of Fib aggregates at 40% and 50% TFE to be prefibrillar and fibrillar respectively. These aggregates possess high thioflavin T fluorescence with a shifted Congo red absorbance. Kinetics of Fib aggregation data at 50% TFE supports nucleation-dependent polymerization mechanism. At 60 and 70% TFE, no aggregation was observed. The inhibition of protein aggregation appears due to weakening of the hydrophobic interactions that were initially stabilizing the intermolecular β-sheet structure in the protein aggregation. The loss of hydrophobic contacts seems to favor the formation of intra-molecular hydrogen bonds over intermolecular hydrogen bonds leads to helix formation. To conclude, protein aggregation is accompanied by the formation of β-sheet conformation, and induction of non-native helical segments in the protein inhibits aggregation. The discrepancy of the secondary structures on aggregation is proposed to stem from the disparity in the nature of the hydrogen bonds and packing of hydrophobic residues of the side chains in the β-sheet and α-helix conformation.
      Graphical abstract image

      PubDate: 2016-05-05T08:45:50Z
       
  • Review: Serial femtosecond crystallography: A revolution in structural
           biology
    • Abstract: Publication date: Available online 30 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jose M. Martin-Garcia, Chelsie E. Conrad, Jesse Coe, Shatabdi Roy-Chowdhury, Petra Fromme
      Macromolecular crystallography at synchrotron sources has proven to be the most influential method within structural biology, producing thousands of structures since its inception. While its utility has been instrumental in progressing our knowledge of structures of molecules, it suffers from limitations such as the need for large, well-diffracting crystals, and radiation damage that can hamper native structural determination. The recent advent of X-ray free electron lasers (XFELs) and their implementation in the emerging field of serial femtosecond crystallography (SFX) has given rise to a remarkable expansion upon existing crystallographic constraints, allowing structural biologists access to previously restricted scientific territory. SFX relies on exceptionally brilliant, micro-focused X-ray pulses, which are femtoseconds in duration, to probe nano/micrometer sized crystals in a serial fashion. This results in data sets comprised of individual snapshots, each capturing Bragg diffraction of single crystals in random orientations prior to their subsequent destruction. Thus structural elucidation while avoiding radiation damage, even at room temperature, can now be achieved. This emerging field has cultivated new methods for nanocrystallogenesis, sample delivery, and data processing. Opportunities and challenges within SFX are reviewed herein.


      PubDate: 2016-05-05T08:45:50Z
       
  • Tropomyosin-binding properties modulate competition between tropomodulin
           isoforms
    • Abstract: Publication date: 15 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 600
      Author(s): Mert Colpan, Natalia A. Moroz, Kevin T. Gray, Dillon A. Cooper, Christian A. Diaz, Alla S. Kostyukova
      The formation and fine-tuning of cytoskeleton in cells are governed by proteins that influence actin filament dynamics. Tropomodulin (Tmod) regulates the length of actin filaments by capping the pointed ends in a tropomyosin (TM)-dependent manner. Tmod1, Tmod2 and Tmod3 are associated with the cytoskeleton of non-muscle cells and their expression has distinct consequences on cell morphology. To understand the molecular basis of differences in the function and localization of Tmod isoforms in a cell, we compared the actin filament-binding abilities of Tmod1, Tmod2 and Tmod3 in the presence of Tpm3.1, a non-muscle TM isoform. Tmod3 displayed preferential binding to actin filaments when competing with other isoforms. Mutating the second or both TM-binding sites of Tmod3 destroyed its preferential binding. Our findings clarify how Tmod1, Tmod2 and Tmod3 compete for binding actin filaments. Different binding mechanisms and strengths of Tmod isoforms for Tpm3.1 contribute to their divergent functional capabilities.


      PubDate: 2016-04-30T08:09:27Z
       
  • AMP-activated kinase α2 deficiency protects mice from
           denervation-induced skeletal muscle atrophy
    • Abstract: Publication date: Available online 29 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yuting Guo, Meng Jin, Yinglong Tang, Ting Wang, Bin Wei, Run Feng, Bing Gong, Huiwen Wang, Guangju Ji, Zhongbing Lu
      AMP-activated protein kinase (AMPK) is a master regulator of skeletal muscle metabolic pathways. Recently, AMPK activation by AICAR has been shown to increase myofibrillar protein degradation in C2C12 myotubes via stimulating autophagy and ubiquitin proteasome system. However, the impact of AMPKα on denervation induced muscle atrophy has not been tested. In this study, we performed sciatic denervation on hind limb muscles in both wild type (WT) and AMPKα2−/− mice. We found that AMPKα was phosphorylated in atrophic muscles following denervation. In addition, deletion of AMPKα2 significantly attenuated denervation induced skeletal muscle wasting and protein degradation, as evidenced by preserved muscle mass and myofiber area, as well as lower levels of ubiquitinated protein, Atrogin-1 and MuRF-1 expression, and LC3-II/I ratio in tibial anterior (TA) muscles. Interestingly, the phosphorylated FoxO3a at Ser253 was significantly decreased in atrophic TA muscles, which was preserved in AMPKα2−/− mice. Collectively, our data support the notion that the activation of AMPKα2 contributes to the atrophic effects of denervation.
      Graphical abstract image

      PubDate: 2016-04-30T08:09:27Z
       
  • A comprehensive review of the role of zinc in normal prostate function and
           metabolism; and its implications in prostate cancer
    • Abstract: Publication date: Available online 27 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Leslie C. Costello, Renty B. Franklin
      The human prostate gland contains extremely high zinc levels; which is due to the specialized zinc-accumulating acinar epithelial of the peripheral zone. These cells evolved for their unique capability to produce and secrete extremely high levels of citrate, which is achieved by the high cellular zinc level on the cell metabolism. This review highlights the specific functional and metabolic alterations that result from the accumulation of the high zinc levels, especially its effects on mitochondrial citrate metabolism and terminal oxidation. The implications of zinc in the development and progression of prostate cancer are described, which is the most consistent hallmark characteristic of prostate cancer. The requirement for decreased zinc resulting from down regulation of ZIP1 to prevent zinc cytotoxicity in the malignant cells is described as an essential early event in prostate oncogenesis. This provides the basis for the concept that an agent (such as the zinc ionophore, clioquinol) that facilitates zinc uptake and accumulation in ZIP1-deficient prostate tumors cells will markedly inhibit tumor growth. In the current absence of an efficacious chemotherapy for advanced prostate cancer, and for prevention of early development of malignancy; a zinc treatment regimen is a plausible approach that should be pursued.


      PubDate: 2016-04-30T08:09:27Z
       
  • What can flies tell us about zinc homeostasis'
    • Abstract: Publication date: Available online 30 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Guiran Xiao, Bing Zhou
      Zinc is an essential micronutrient for all organisms. For multicellular organisms, zinc uptake, storage, distribution and export are tightly regulated at both cellular and organismal levels, to cope with the multiple requirements versus the toxicity of the metal ion. During the past decade, the fruit fly Drosophila melanogaster has become an important model organism for the elucidation of metazoan zinc homeostasis. This review describes our current knowledge of various zinc transporters in Drosophila, with an emphasis on the process of dietary zinc uptake in the fly. We also discuss how Drosophila was used as a model to facilitate our understanding of the role of zinc in neurodegenerative diseases.


      PubDate: 2016-04-30T08:09:27Z
       
  • Investigation of plasma induced electrical and chemical factors and their
           contribution processes to plasma gene transfection
    • Abstract: Publication date: Available online 29 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Masafumi Jinno, Yoshihisa Ikeda, Hideki Motomura, Yugo Kido, Susumu Satoh
      This study have been done to know what kind of factors in plasmas and processes on cells induce plasma gene transfection. We evaluated the contribution weight of three groups of the effects and processes, i.e. electrical, chemical and biochemical ones, inducing gene transfection. First, the laser produced plasma (LPP) was employed to estimate the contribution of the chemical factors. Second, liposomes were fabricated and employed to evaluate the effects of plasma irradiation on membrane under the condition without biochemical reaction. Third, the clathrin-dependent endocytosis, one of the biochemical processes was suppressed. It becomes clear that chemical factors (radicals and reactive oxygen/nitrogen species) do not work by itself alone and electrical factors (electrical current, charge and field) are essential to plasma gene transfection. It turned out the clathrin-dependent endocytosis is the process of the transfection against the 60% in all the transfected cells. The endocytosis and electrical poration are dominant in plasma gene transfection, and neither permeation through ion channels nor chemical poration is dominant processes. The simultaneous achievement of high transfection efficiency and high cell survivability is attributed to the optimization of the contribution weight among three groups of processes by controlling the weight of electrical and chemical factors.
      Graphical abstract image

      PubDate: 2016-04-30T08:09:27Z
       
  • Low-temperature atmospheric-pressure plasma sources for plasma medicine
    • Abstract: Publication date: Available online 22 April 2016
      Source:Archives of Biochemistry and Biophysics
      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: 2016-04-26T06:48:15Z
       
  • An intramolecular disulfide bond designed in myoglobin fine-tunes both
           protein structure and peroxidase activity
    • Abstract: Publication date: Available online 23 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Lei-Bin Wu, Hong Yuan, Hu Zhou, Shu-Qin Gao, Chang-Ming Nie, Xiangshi Tan, Ge-Bo Wen, Ying-Wu Lin
      Disulfide bond plays crucial roles in stabilization of protein structure and in fine-tuning protein functions. To explore an approach for rational heme protein design, we herein rationally introduced a pair of cysteines (F46C/M55C) into the scaffold of myoglobin (Mb), mimicking those in native neuroglobin. Molecular modeling suggested that it is possible for Cys46 and Cys55 to form an intramolecular disulfide bond, which was confirmed experimentally by ESI-MS analysis, DTNB reaction and CD spectrum. Moreover, it was shown that the spontaneously formed disulfide bond of Cys46-Cys55 fine-tunes not only the heme active site structure, but also the protein functions. The substitution of Phe46 with Ser46 in F46S Mb destabilizes the protein while facilitates H2O2 activation. Remarkably, the formation of an intramolecular disulfide bond of Cys46-Cys55 in F46C/M55C Mb improves the protein stability and regulates the heme site to be more favorable for substrate binding, resulting in enhanced peroxidase activity. This study provides valuable information of structure-function relationship for heme proteins regulated by an intramolecular disulfide bond, and also suggests that construction of such a covalent bond is useful for design of functional heme proteins.
      Graphical abstract image

      PubDate: 2016-04-26T06:48:15Z
       
  • The biological inorganic chemistry of zinc ions
    • Abstract: Publication date: Available online 23 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Artur Krężel, Wolfgang Maret
      The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: Zn(II). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the “mobile” zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide (ZnO). In most investigations, reference is made to zinc or Zn2+ without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn2+ differs from s-block cations such as Ca2+ with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is important in zinc biochemistry and for biological recognition as a variety of low molecular weight zinc complexes have already been implicated in biological processes, e.g. with ATP, glutathione, citrate, ethylenediaminedisuccinic acid, nicotianamine, or bacillithiol.


      PubDate: 2016-04-26T06:48:15Z
       
  • Mechanistic insights into the first Lygus-active β-pore forming
           protein
    • Abstract: Publication date: 15 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 600
      Author(s): Agoston Jerga, Danqi Chen, Chunfen Zhang, Jinping Fu, Jean-Louis K. Kouadio, Yanfei Wang, Stephen M.G. Duff, Jennifer E. Howard, Timothy J. Rydel, Artem G. Evdokimov, Parthasarathy Ramaseshadri, Adam Evans, Renata Bolognesi, Yoonseong Park, Jeffrey A. Haas
      The cotton pests Lygus hesperus and Lygus lineolaris can be controlled by expressing Cry51Aa2.834_16 in cotton. Insecticidal activity of pore-forming proteins is generally associated with damage to the midgut epithelium due to pores, and their biological specificity results from a set of key determinants including proteolytic activation and receptor binding. We conducted mechanistic studies to gain insight into how the first Lygus-active β-pore forming protein variant functions. Biophysical characterization revealed that the full-length Cry51Aa2.834_16 was a stable dimer in solution, and when exposed to Lygus saliva or to trypsin, the protein underwent proteolytic cleavage at the C-terminus of each of the subunits, resulting in dissociation of the dimer to two separate monomers. The monomer showed tight binding to a specific protein in Lygus brush border membranes, and also formed a membrane-associated oligomeric complex both in vitro and in vivo. Chemically cross-linking the β-hairpin to the Cry51Aa2.834_16 body rendered the protein inactive, but still competent to compete for binding sites with the native protein in vivo. Our study suggests that disassociation of the Cry51Aa2.834_16 dimer into monomeric units with unoccupied head-region and sterically unhindered β-hairpin is required for brush border membrane binding, oligomerization, and the subsequent steps leading to insect mortality.


      PubDate: 2016-04-22T16:39:29Z
       
  • Low sequence identity but high structural and functional conservation: The
           case of Hsp70/Hsp90 organizing protein (Hop/Sti1) of Leishmania
           braziliensis
    • Abstract: Publication date: Available online 19 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Fernanda A.H. Batista, Thiago V. Seraphim, Clelton A. Santos, Marisvanda R. Gonzaga, Leandro R.S. Barbosa, Carlos H.I. Ramos, Júlio C. Borges
      Parasites belonging to the genus Leishmania are subjected to extensive environmental changes during their life cycle; molecular chaperones/co-chaperones act as protagonists in this scenario to maintain cellular homeostasis. Hop/Sti1 is a co-chaperone that connects the Hsp90 and Hsp70 systems, modulating their ATPase activities and affecting the fate of client proteins because it facilitates their transfer from the Hsp70 to the Hsp90 chaperone. Hop/Sti1 is one of the most prevalent co-chaperones, highlighting its importance despite the relatively low sequence identity among orthologue proteins. This multi-domain protein comprises three tetratricopeptides domains (TPR1, TPR2A and TPR2B) and two Asp/Pro-rich domains. Given the importance of Hop/Sti1 for the chaperone system and for Leishmania protozoa viability, the Leishmania braziliensis Hop (LbHop) and a truncated mutant (LbHopTPR2AB) were characterized. Structurally, both proteins are α-helix-rich and highly elongated monomeric proteins. Functionally, they inhibited the ATPase activity of L. braziliensis Hsp90 (LbHsp90) to a similar extent, and the thermodynamic parameters of their interactions with LbHsp90 were similar, indicating that TPR2A-TPR2B forms the functional center for the LbHop interaction with LbHsp90. These results highlight the structural and functional similarity of Hop/Sti1 proteins, despite their low sequence conservation compared to the Hsp70 and Hsp90 systems, which are phylogenetic highly conserved.
      Graphical abstract image

      PubDate: 2016-04-22T16:39:29Z
       
  • Tanshinone ⅡA inhibits human esophageal cancer cell growth through
           miR-122-mediated PKM2 down-regulation
    • Abstract: Publication date: 15 May 2016
      Source:Archives of Biochemistry and Biophysics, Volume 598
      Author(s): Hong-Sheng Zhang, Feng-Juan Zhang, Hu Li, Yang Liu, Guang-Yuan Du, Ying-Hui Huang
      Pyruvate kinase M2 (PKM2) plays a pivotal role in the growth, survival and metabolic reprogramming of cancer cells. Here, we presented for the first time that tanshinone ⅡA inhibited human esophagus cancer cell growth through miR-122-mediated PKM2 down-regulation pathway. Tanshinone ⅡA inhibited cell proliferation and induced cell cycle arrest in S phase in human Ec109 cells. As expected, tanshinone ⅡA down-regulated PKM2 mRNA and protein expression in Ec109 cells. Given these findings, we further investigated microRNAs regulation of PKM2 and confirmed miR-122 for targeting PKM2. Moreover, we found that tanshinone ⅡA-induced up-regulation of miR-122 expression inhibited PKM2 expression in Ec109 cells. Meanwhile, tanshinone ⅡA inhibited proliferation through miR122-medated PKM2 down-regulation. It was demonstrated that the anticancer activity of tanshinone ⅡA was targeted at metabolic regulation of miR-122/PKM2 in human esophagus cancer cells. Taken together, our results revealed tanshinone ⅡA targeting at PKM2-mediated metabolic reprogramming play an important role in inhibition of esophageal cancer cell growth.


      PubDate: 2016-04-17T16:33:48Z
       
  • Nuclear factor-κB–dependent microRNA-130a upregulation promotes
           cervical cancer cell growth by targeting phosphatase and tensin homolog
    • Abstract: Publication date: 15 May 2016
      Source:Archives of Biochemistry and Biophysics, Volume 598
      Author(s): Yeqian Feng, Shenghua Zhou, Guiyuan Li, Chunhong Hu, Wen Zou, Haixia Zhang, Lili Sun
      Nuclear factor-κB (NF-κB) may activate a series of gene transcription control cellular signaling pathways whose products are components in a wide range of biological processes. MicroRNAs, a group of non-coding endogenous ones, may regulate gene expression and plays specific roles in tumorigenesis. Using human cervical cancer cell lines, we explored whether NF-κB regulates the expression of microRNA-130a (miR-130a) through binding elements in the miR-130a promoter region. We found that miR-130a accelerates cervical cancer cell proliferation by targeting the phosphatase and tensin homolog on chromosome 10 (PTEN). Further, NF-κB activates both HeLa and CaSki cell growth by upregulating miR-130a. In addition, by targeting PTEN 3′ untranslated region, miR-130a might increase cell growth and initiate protein kinase B (AKT) pathway activation. Lastly, PTEN protein was upregulated in response to NF-κB overexpression and downregulated in response to NF-κB inhibition. Compared to total AKT protein level, p-AKT was downregulated by NF-κB overexpression while upregulated by NF-κB inhibition, indicating PTEN pathway activated and affected by NF-κB. Taken together, our findings shed new light on the NF-κB/miR-130a/PTEN pathway in cervical cancer and add new insight regarding the carcinogenesis of cervical cancer.


      PubDate: 2016-04-17T16:33:48Z
       
  • Oxidative hemoglobin reactions: Applications to drug metabolism
    • Abstract: Publication date: Available online 16 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Tatyana Spolitak, Paul F. Hollenberg, David P. Ballou
      Hb is a protein with multiple functions, acting as an O2 transport protein, and having peroxidase and oxidase activities with xenobiotics that lead to substrate radicals. However, there is a lack of evidence for intermediates involved in these reactions of Hb with redox-active compounds, including those with xenobiotics such as drugs, chemical carcinogens, and sulfides. In particular, questions exist as to what intermediates participate in reactions of either metHb or oxyHb with sulfides. The studies presented here elaborate kinetics and intermediates involved in the reactions of Hb with oxidants (H2O2 and mCPBA), and they demonstrate the formation of high valent intermediates, providing insights into mechanistic issues of sulfur and drug oxidations. Overall, we propose generalized mechanisms that include peroxidatic reactions using H2O2 generated from the autooxidation of oxyHb, with involvement of substrate radicals in reactions of Hb with oxidizable drugs such as metyrapone or 2,4-dinitrophenylhydrazine and with sulfides. We identify ferryl intermediates (with a Soret band at 407 nm) in oxidative reactions with all of the above-mentioned reactions. These spectral properties are consistent with a protonated ferryl heme, such as Cpd II or Cpd ES-like species (Spolitak et al., JIB, 2006, 100, 2034–2044). Mechanism(s) of Hb oxidative reactions are discussed.
      Graphical abstract image

      PubDate: 2016-04-17T16:33:48Z
       
  • Dimethyl ester of bilirubin exhibits anti-inflammatory activity through
           
    • Abstract: Publication date: Available online 6 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Vikram Joshi, M. Umashankara, Chandrasekaran Ramakrishnan, Ankanahalli N. Nanjaraj Urs, Suvilesh Kanve Nagaraj, Devadasan Velmurugan, Kanchugarakoppal S. Rangappa, Bannikuppe Sannanaik Vishwanath
      Overproduction of arachidonic acid (AA) mediated by secretory phospholipase A2 group IIA (sPLA2IIA) is a hallmark of many inflammatory disorders. AA is subsequently converted into pro-inflammatory eicosanoids through 5-lipoxygenase (5-LOX) and cyclooxygenase-1/2 (COX-1/2) activities. Hence, inhibition of sPLA2IIA, 5-LOX and COX-1/2 activities is critical in regulating inflammation. We have previously reported unconjugated bilirubin (UCB), an endogenous antioxidant, as sPLA2IIA inhibitor. However, lipophilic UCB gets conjugated in liver with glucuronic acid into hydrophilic conjugated bilirubin (CB). Since hydrophobicity is pre-requisite for sPLA2IIA inhibition, conjugation reduces the efficacy of UCB. In this regard, UCB was chemically modified and derivatives were evaluated for sPLA2IIA, 5-LOX and COX-1/2 inhibition. Among the derivatives, BD1 (dimethyl ester of bilirubin) exhibited ∼ 3 fold greater inhibitory potency towards sPLA2IIA compared to UCB. Both UCB and BD1 inhibited human 5-LOX and COX-2 activities; however only BD1 inhibited AA induced platelet aggregation. Molecular docking studies demonstrated BD1 as better inhibitor of aforesaid enzymes than UCB and other endogenous antioxidants. These data suggest that BD1 exhibits strong anti-inflammatory activity through inhibition of AA cascade enzymes which is of great therapeutic importance.
      Graphical abstract image

      PubDate: 2016-04-10T00:03:59Z
       
  • Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic
           arteries through modulating the angiotensin-converting enzyme
           2-angiotensin-(1–7)-Mas receptor axis
    • Abstract: Publication date: Available online 2 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yonghong Li, Shanglang Cai, QixinWang, Jingwei Zhou, Bo Hou, Haichu Yu, Zhiming Ge, Renyan Guan, Xu Liu
      The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1–7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1–7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P < 0.05 or < 0.01). Additionally, the p-ERK protein expression was increased (P < 0.01). Treatment with valsartan significantly increased the angiotensin-(1–7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P < 0.05 or < 0.01). These results suggest that valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1–7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways.
      Graphical abstract image

      PubDate: 2016-04-06T08:57:42Z
       
  • Reflections on the role of senescence during development and aging
    • Abstract: Publication date: Available online 6 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): F. Triana-Martínez, G. Pedraza-Vázquez, L.A. Maciel-Barón, M. Königsberg
      New and stimulating results have challenged the concept that cellular senescence might not be synonymous with aging. It is indisputable that during aging, senescent cell accumulation has an impact on organismal health. Nevertheless, senescent cells are now known to display physiological roles during embryonic development, during wound healing repair and as a cellular response to stress. The fact that senescence has been found in cells that did not attain their maximal round of replications, nor have metabolic alterations or DNA damage, also challenges the paradigm that senescence is cellular aging, and it is in favor of the idea that cellular senescence is a phenomenon that has a function by itself. Therefore, in order to understand this phenomenon it is important to analyze the relationship between senescence and other cellular responses that have many features in common, such as apoptosis, cancer and autophagy, particularly highlighting their role during development and adulthood.
      Graphical abstract image

      PubDate: 2016-04-06T08:57:42Z
       
  • A multiplexed targeted assay for high-throughput quantitative analysis of
           serum methylamines by ultra performance liquid chromatography coupled to
           high resolution mass spectrometry
    • Abstract: Publication date: Available online 30 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hanane Kadar, Justine Dubus, Jérémie Dutot, Lyamine Hedjazi, Suman Srinivasa, Kathleen V. Fitch, Steven K. Grinspoon, Jeremy K. Nicholson, Marc-Emmanuel Dumas, Dominique Gauguier
      Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable “methylamine panel” method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and L-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS). Metabolite separation was carried out on a HILIC stationary phase. For all metabolites, the assay was linear in the range of 0.25 to 12.5μmol/L and enabled to reach limit of detection of about 0.10μmol/L. Relative standard deviations were below 16% for the three levels of concentrations. We demonstrated the strong reliability and robustness of the method, which was applied to serum samples from healthy individuals to establish the range of concentrations of the metabolites and their correlation relationships and detect gender differences. Our data provide original information for implementing in a clinical environment a MS-based diagnostic method with potential for targeted metabolic screening of patients at risk of cardiometabolic diseases.


      PubDate: 2016-04-02T07:39:03Z
       
  • Incorporation of phosphate into glycogen by glycogen synthase
    • Abstract: Publication date: Available online 29 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Christopher J. Contreras, Dyann M. Segvich, Krishna Mahalingan, Vimbai M. Chikwana, Terence L. Kirley, Thomas D. Hurley, Anna A. DePaoli-Roach, Peter J. Roach
      The storage polymer glycogen normally contains small amounts of covalently attached phosphate as phosphomonoesters at C2, C3 and C6 atoms of glucose residues. In the absence of the laforin phosphatase, as in the rare childhood epilepsy Lafora disease, the phosphorylation level is elevated and is associated with abnormal glycogen structure that contributes to the pathology. Laforin therefore likely functions in vivo as a glycogen phosphatase. The mechanism of glycogen phosphorylation is less well-understood. We have reported that glycogen synthase incorporates phosphate into glycogen via a rare side reaction in which glucose-phosphate rather than glucose is transferred to a growing polyglucose chain (Tagliabracci et al. (2011) Cell Metab 13, 274-282). We proposed a mechanism to account for phosphorylation at C2 and possibly at C3. Our results have since been challenged (Nitschke et al. (2013) Cell Metab 17, 756-767). Here we extend the evidence supporting our conclusion, validating the assay used for the detection of glycogen phosphorylation, measurement of the transfer of 32P from [β-32P]UDP-glucose to glycogen by glycogen synthase. The 32P associated with the glycogen fraction was stable to ethanol precipitation, SDS-PAGE and gel filtration on Sephadex G50. The 32P-signal was not affected by inclusion of excess unlabeled UDP before analysis or by treatment with a UDPase, arguing against the signal being due to contaminating [β-32P]UDP generated in the reaction. Furthermore, [32P]UDP did not bind non-covalently to glycogen. The 32P associated with glycogen was released by laforin treatment, suggesting that it was present as a phosphomonoester. The conclusion is that glycogen synthase can mediate the introduction of phosphate into glycogen, thereby providing a possible mechanism for C2, perhaps C3, phosphorylation.


      PubDate: 2016-04-02T07:39:03Z
       
  • Cyp1b1 affects external control of mouse hepatocytes, fatty acid
           homeostasis and signaling involving HNF4α and PPARα
    • Abstract: Publication date: Available online 29 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Justin R. Bushkofsky, Meghan Maguire, Michele Campaigne Larsen, Yee Hoon Fong, Colin R. Jefcoate
      Cytochrome P450 1b1 (Cyp1b1) is expressed in endothelia, stellate cells and pre-adipocytes, but not hepatocytes. Deletion alters liver fatty acid metabolism and prevents obesity and hepatic steatosis. This suggests a novel extra-hepatocyte regulation directed from cells that express Cyp1b1. To characterize these mechanisms, microarray gene expression was analyzed in livers of normal and congenic Cyp1b1-ko C57BL/6J mice fed either low or high fat diets. Cyp1b1-ko gene responses indicate suppression of endogenous PPARα activity, a switch from triglyceride storage to mitochondrial fatty acid oxidation and decreased oxidative stress. Many gene responses in Cyp1b1-ko are sexually dimorphic and correspond to increased activity of growth hormone mediated by HNF4α. Male responses stimulated by GH pulses are enhanced, whereas responses that decline exhibit further suppression, including Cyp regulation by PPARα, CAR and PXR. These effects of Cyp1b1 deletion overlap with effects caused by deletion of the small heterodimeric partner, a suppressor of these nuclear factors. Redirection of gene expression associated with liver fat homeostasis in Cyp1b1-ko mice that directs hypothalamic control of GH and leptin. Cyp1b1-ko suppresses neonatal Scd1 and delays adult maturation of dimorphic GH/HNF4α signaling. Alternatively, deletion may diminish hypothalamic metabolism of estradiol, which establishes adult GH regulation.


      PubDate: 2016-04-02T07:39:03Z
       
  • Determinants of the pKa values of ionizable residues in an intrinsically
           disordered protein
    • Abstract: Publication date: Available online 1 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): José L. Neira, Bruno Rizzuti, Juan L. Iovanna
      Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes; in humans, they are often associated with diseases. The protein NUPR1 is a multifunctional IDP involved in the development and progression of pancreatic cancer; therefore, it constitutes a target for drug design. In an effort to contribute to the understanding of the conformational features of NUPR1 and to provide clues on amino acid interactions in disordered states of proteins, we measured the pK a values of all its acidic groups (aspartic and glutamic residues, and backbone C terminus) by using NMR spectroscopy at low (100 mM) and high (500 mM) NaCl concentration. At low ionic strength, the pK a values were similar to those reported for random-coil models, except for Glu18 and Asp19, suggesting electrostatic interactions around these residues. Molecular modelling and simulation indicate an additional, significant role of nearby proline residues in determining the polypeptide conformational features and water accessibility in the region around Glu18, modulating the titration properties of these amino acids. In the other acidic residues of NUPR1, the small deviations of pK a values (compared to those expected for a random-coil) are likely due to electrostatic interactions with charged adjacent residues, which should be reduced at high NaCl concentrations. In fact, at high ionic strength, the pK a values of the aspartic residues were similar to those in a random coil, but there were still small differences for those of glutamic acids, probably due to hydrogen-bond formation. The overall findings suggest that local interactions and hydrophobic effects play a major role in determining the electrostatic features of NUPR1, whereas long-range charge contributions appear to be of lesser importance.
      Graphical abstract image

      PubDate: 2016-04-02T07:39:03Z
       
  • Acetylome study in mouse adipocytes identifies targets of SIRT1
           deacetylation in chromatin organization and RNA processing
    • Abstract: Publication date: Available online 26 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sun-Yee Kim, Choon Kiat Sim, Hui Tang, Weiping Han, Kangling Zhang, Feng Xu
      SIRT1 is a key protein deacetylase that regulates cellular metabolism through lysine deacetylation on both histones and non-histone proteins. Lysine acetylation is a wide-spread post-translational modification found on many regulatory proteins and it plays an essential role in cell signaling, transcription and metabolism. In mice, SIRT1 has known protective functions during high-fat diet but the acetylome regulated by SIRT1 in adipocytes is not completely understood. Here we conducted acetylome analyses in murine adipocytes treated with small-molecule modulators that inhibit or activate the deacetylase activity of SIRT1. We identified a total of 302 acetylated peptides from 78 proteins in this study. From the list of potential SIRT1 targets, we selected seven candidates and further verified that six of them can be deacetylated by SIRT1 in-vitro. Among them, half of the SIRT1 targets are involved in regulating chromatin structure and the other half is involved in RNA processing. Our results provide a resource for further SIRT1 target validation in fat cells and suggest a potential role of SIRT1 in the regulation of chromatin structure and RNA processing, which may possibly extend to other cell types as well.


      PubDate: 2016-03-28T07:30:30Z
       
  • Aβ40 has a subtle effect on Aβ42 protofibril formation, but to a
           lesser degree than Aβ42 concentration, in Aβ42/Aβ40
           mixtures
    • Abstract: Publication date: Available online 21 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Shana E. Terrill-Usery, Benjamin A. Colvin, Richard E. Davenport, Michael R. Nichols
      Recent findings suggest that the senile plaques in Alzheimer’s disease may contain soluble amyloid-β peptide (Aβ) fibril precursors along with insoluble fibrils. These soluble Aβ species, including oligomers and protofibrils, have been well-studied in vitro and are formed via non-covalent self-assembly of Aβ monomers. While both 40- and 42-residue forms of Aβ are observed in the human body, the majority of the Aβ aggregation work has been conducted on Aβ42 or Aβ40 separately, with relatively few investigations of mixtures. In order to study the effect of different combinations of Aβ40 and Aβ42 on protofibril formation, mixtures of either dry solid peptide, or purified Aβ40 and Aβ42 monomer solutions were mixed together and protofibril/monomer distributions were quantified. Increases in the Aβ42/Aβ40 ratio increased protofibril formation but the presence of Aβ40 in the mixed Aβ solutions had a significant negative impact on protofibril formation compared to equivalent solutions of pure Aβ42. Protofibril size was less affected, but β-sheet structure increased with protofibrils formed from higher Aβ42/Aβ40 ratio solutions. Direct measurement of Aβ42/Aβ40 ratios by C-terminal-selective ELISA found very little Aβ40 incorporated into protofibrils. The cumulative data emphasizes the critical importance of Aβ42, yet establishes Aβ40 as a regulator of Aβ42 aggregation.


      PubDate: 2016-03-24T07:12:34Z
       
  • Glutamine protects cardiomyocytes from hypoxia/reoxygenation injury under
           high glucose conditions through inhibition of the transforming growth
           factor-β1-Smad3 pathway
    • Abstract: Publication date: Available online 3 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hong Zhang, Yong-chun Cui, Kai Li, Bai-qing Yang, Xiao-peng Liu, Dong Zhang, Hao Li, Ai-li Wu, Yue Tang
      Activation of transforming growth factor-β1 (TGF-β1)-Smad3 pathway aggravates myocardial ischemia/reperfusion injury (IRI). We previously showed that glutamine (Gln) protects cardiomyocytes from hypoxia/ reoxygenation (H/R) injury under high glucose (HG) conditions. The aim of this study was to investigate whether Gln exerts its protective effect in H/R via inhibiting TGF-β1-Smad3 pathway. In vitro, H9c2 rat cardiomyocytes were treated with Gln with HG (33 mM) and/or H/R. We also performed in vivo experiments in which we treated normal and diabetic rats with Gln or solvent control following IRI. We assessed protein levels of TGF-β1, total Smad3, phosphorylated (p)-Smad3 and cleaved caspase-3 in H9c2 cells and rat myocardium by Western blotting. H9c2 cells treated with HG + H/R exhibited high apoptosis rates, as well as a highly activated TGF-β1-Smad3 pathway. TGF-β1 receptor inhibitor (SB431542) or Smad3 inhibitor (SIS3) reduced HG + H/R induced apoptosis. Similarly, Gln supplementation alleviated apoptosis and decreased p-Smad3 levels. However, Gln’s protective effect was significantly weakened by TGF-β1. Diabetic rats treated with Gln had improved hemodynamics, smaller infarct size after IRI, and a significant decrease in TGF-β1-Smad3 pathway activation. We conclude that Gln inhibits HG + H/R induced activation of the TGF-β1-Smad3 pathway and decreases cell apoptosis in cardiomyocytes.


      PubDate: 2016-03-05T16:02:09Z
       
  • Understanding the importance of conservative hypothetical protein
           LdBPK_070020 in Leishmania donovani and its role in subsistence of the
           parasite
    • Abstract: Publication date: Available online 27 February 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ruchika Bhardwaj, Ritesh Kumar, Sanjeev Kumar Singh, Chandrabose Selvaraj, Vikash Kumar Dubey
      The genome of Leishmania donovani, the causative agent of visceral leishmaniasis, codes for approximately 65% of both conserved and non-conserved hypothetical proteins. Studies on ‘conserved hypothetical’ proteins are expected to reveal not only new and crucial aspects of Leishmania biochemistry, but it could also lead to discovery of novel drug candidates. Conserved hypothetical protein, LdBPK_070020, is a 31.14 kDa protein, encoded by an 810 bp gene. BLAST analysis of LdBPK_070020, performed against NCBI non-redundant database, showed 80-99% similarity with conserved hypothetical proteins of Leishmania belonging to other species. Using homologues recombination method, we have performed gene knockout of LdBPK_070020 and effects of the same were investigated on the parasite. The gene knocked out strain shows significant retardation in growth with respect to wild type. Details biochemical studies indicated towards important role of LdBPK_070020 in the parasite survival and growth.
      Graphical abstract image

      PubDate: 2016-02-29T15:48:49Z
       
  • Spectroscopic and QM/MM Investigations of Chloroperoxidase Catalyzed
           Degradation of Orange G
    • Abstract: Publication date: Available online 27 February 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rui Zhang, Qinghao He, Yi Huang, Xiaotang Wang
      Chloroperoxidase (CPO), a heme-thiolate protein, from Caldariomyces fumago catalyzes a plethora of reactions including halogenation, dismutation, epoxidation, and oxidation. Although all CPO-catalyzed reactions go through a common intermediate, compound I, different mechanisms are followed in subsequent transformations. To understand the mechanism of CPO-catalyzed halide-dependent degradation of orange G, the role of halide and pH was systematically investigated. It is revealed that formation and protonation of compound X, a long-sought after hypochlorite heme adduct intermediate existed during CPO-catalyzed halide-dependent reactions, significantly lowers the reaction barrier and increases the efficiency of CPO-catalyzed orange G degradation. The extremely acidic optimal reaction pH suggests the protonation of a residue, presumably, Glu 183 in CPO catalysis. Halide dependent studies showed that K cat is higher in the presence of Br- than in the presence of Cl-. The degradation products of orange G indicate the cleavage at a single position of orange G, demonstrating a high regioselectivity of CPO-catalyzed degradation. Based on our kinetic, NMR and QM/MM studies, the mechanism of CPO-catalyzed orange G degradation was proposed.
      Graphical abstract image

      PubDate: 2016-02-29T15:48:49Z
       
  • A review of solute encapsulating nanoparticles used as delivery systems
           with emphasis on branched amphipathic peptide capsules
    • Abstract: Publication date: Available online 27 February 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sheila de M. Barros, Susan K. Whitaker, Pinakin Sukthankar, L. Adriana Avila, Sushanth Gudlur, Matt Warner, Eduardo I.C. Beltrão, John M. Tomich
      Various strategies are being developed to improve delivery and increase the biological half-lives of pharmacological agents. To address these issues, drug delivery technologies rely on different nano-sized molecules including: lipid vesicles, viral capsids and nano-particles. Peptides are a constituent of many of these nanomaterials and overcome some limitations associated with lipid-based or viral delivery systems, such as tune-ability, stability, specificity, inflammation, and antigenicity. This review focuses on the evolution of bio-based drug delivery nanomaterials that self-assemble forming vesicles/capsules. While lipid vesicles are preeminent among the structures; peptide-based constructs are emerging, in particular peptide bilayer delimited capsules. The novel biomaterial— Branched Amphiphilic Peptide Capsules (BAPCs) display many desirable properties. These nano-spheres are comprised of two branched peptides— bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK, designed to mimic diacyl-phosphoglycerides in molecular architecture. They undergo supramolecular self-assembly and form solvent-filled, bilayer delineated capsules with sizes ranging from 20 nm to 2 microns depending on annealing temperatures and time. They are able to encapsulate different fluorescent dyes, therapeutic drugs, radionuclides and even small proteins. While sharing many properties with lipid vesicles, the BAPCs are much more robust. They have been analyzed for stability, size, cellular uptake and localization, intra-cellular retention and, bio-distribution both in culture and in vivo.


      PubDate: 2016-02-29T15:48:49Z
       
 
 
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