for Journals by Title or ISSN
for Articles by Keywords
  Subjects -> BIOLOGY (Total: 2968 journals)
    - BIOCHEMISTRY (230 journals)
    - BIOENGINEERING (105 journals)
    - BIOLOGY (1418 journals)
    - BIOPHYSICS (46 journals)
    - BIOTECHNOLOGY (212 journals)
    - BOTANY (215 journals)
    - CYTOLOGY AND HISTOLOGY (26 journals)
    - ENTOMOLOGY (63 journals)
    - GENETICS (160 journals)
    - MICROBIOLOGY (254 journals)
    - MICROSCOPY (10 journals)
    - ORNITHOLOGY (26 journals)
    - PHYSIOLOGY (69 journals)
    - ZOOLOGY (134 journals)

BIOCHEMISTRY (230 journals)                  1 2     

Showing 1 - 0 of 0 Journals sorted alphabetically
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Central Science     Open Access   (Followers: 5)
ACS Chemical Biology     Full-text available via subscription   (Followers: 199)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 16)
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: 9)
Advances in Biological Chemistry     Open Access   (Followers: 7)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 16)
African Journal of Biochemistry Research     Open Access   (Followers: 1)
African Journal of Chemical Education     Open Access   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
American Journal of Biochemistry     Open Access   (Followers: 7)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 64)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 14)
American Journal of Polymer Science     Open Access   (Followers: 23)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical Biochemistry     Hybrid Journal   (Followers: 143)
Angiogenesis     Hybrid Journal   (Followers: 3)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 52)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 12)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 44)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 17)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 6)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 21)
Archives of Insect Biochemistry and Physiology     Hybrid Journal  
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Avicenna Journal of Medical Biochemistry     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 19)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 4)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 13)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 26)
Biochemical Pharmacology     Hybrid Journal   (Followers: 9)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 4)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 243)
Biochemistry & Pharmacology : Open Access     Open Access   (Followers: 3)
Biochemistry & Physiology : Open Access     Open Access  
Biochemistry (Moscow)     Hybrid Journal   (Followers: 4)
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology     Hybrid Journal   (Followers: 3)
Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry     Hybrid Journal   (Followers: 3)
Biochemistry and Biophysics Reports     Open Access  
Biochemistry and Cell Biology     Full-text available via subscription   (Followers: 14)
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: 6)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 8)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 16)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 6)
Biochimie     Hybrid Journal   (Followers: 7)
Biochimie Open     Open Access  
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 30)
BioDrugs     Full-text available via subscription   (Followers: 8)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 11)
Biogeochemistry     Hybrid Journal   (Followers: 11)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 24)
Biomaterials Research     Open Access   (Followers: 4)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Hybrid Journal   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 24)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44)
Bitácora Digital     Open Access  
BMC Biochemistry     Open Access   (Followers: 14)
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca : Food Science and Technology     Open Access  
Carbohydrate Polymers     Hybrid Journal   (Followers: 8)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 5)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 5)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
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: 31)
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  
Clinica Chimica Acta     Hybrid Journal   (Followers: 36)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 19)
Clinical Chemistry     Full-text available via subscription   (Followers: 68)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 61)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 5)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 7)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 3)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 11)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 5)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 15)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 25)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 6)
DNA Barcodes     Open Access  
Doklady Biochemistry and Biophysics     Hybrid Journal   (Followers: 1)
Doklady Chemistry     Hybrid Journal  
Egyptian Journal of Biochemistry and Molecular Biology     Full-text available via subscription  
FABICIB     Open Access  
FEBS Letters     Hybrid Journal   (Followers: 59)
FEBS Open Bio     Open Access   (Followers: 3)
Fish Physiology and Biochemistry     Hybrid Journal   (Followers: 4)
Food & Function     Full-text available via subscription   (Followers: 5)
Foundations of Modern Biochemistry     Full-text available via subscription  
Free Radicals and Antioxidants     Full-text available via subscription   (Followers: 4)
Frontiers in Molecular Biosciences     Open Access   (Followers: 2)
Frontiers in Natural Product Chemistry     Hybrid Journal  
Global Biogeochemical Cycles     Full-text available via subscription   (Followers: 12)
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   (Followers: 1)
Indonesian Biomedical Journal     Open Access  
Insect Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 3)
International Journal of Biochemistry & Cell Biology     Hybrid Journal   (Followers: 7)
International Journal of Biochemistry and Biophysics     Open Access   (Followers: 1)
International Journal of Biological Chemistry     Open Access   (Followers: 4)
International Journal of Biomedical Nanoscience and Nanotechnology     Hybrid Journal   (Followers: 6)
International Journal of Food Contamination     Open Access  
International Journal of Plant Physiology and Biochemistry     Open Access  
International Journal of Plant Research     Open Access   (Followers: 3)
International Journal of Secondary Metabolite     Open Access   (Followers: 1)
Invertebrate Immunity     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 5)
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: 43)
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 178)
Journal of Biomaterials Science, Polymer Edition     Hybrid Journal   (Followers: 9)
Journal of Carbohydrate Chemistry     Hybrid Journal   (Followers: 7)
Journal of Cellular Biochemistry     Hybrid Journal   (Followers: 5)
Journal of Chemical Biology     Hybrid Journal   (Followers: 1)
Journal of Chemical Neuroanatomy     Hybrid Journal  
Journal of Clinical Lipidology     Hybrid Journal   (Followers: 1)
Journal of Comparative Physiology B : Biochemical, Systemic, and Environmental Physiology     Hybrid Journal   (Followers: 4)
Journal of Drug Discovery and Therapeutics     Open Access   (Followers: 1)
Journal of Enzyme Inhibition and Medicinal Chemistry     Hybrid Journal   (Followers: 4)
Journal of Evolutionary Biochemistry and Physiology     Hybrid Journal  
Journal of Food and Drug Analysis     Open Access  
Journal of Forensic Toxicology and Pharmacology     Hybrid Journal   (Followers: 3)
Journal of Inborn Errors of Metabolism and Screening     Open Access  
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 6)
Journal of Investigational Biochemistry     Open Access   (Followers: 2)
Journal of Medical and Biomedical Sciences     Open Access  
Journal of Medical Biochemistry     Open Access   (Followers: 4)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Molecular Biochemistry     Open Access   (Followers: 3)
Journal of Molecular Diagnostics     Hybrid Journal   (Followers: 7)
Journal of Neurochemistry     Hybrid Journal   (Followers: 3)
Journal of Nutritional Biochemistry     Hybrid Journal   (Followers: 7)
Journal of Pediatric Biochemistry     Hybrid Journal   (Followers: 1)
Journal of Peptide Science     Hybrid Journal   (Followers: 23)
Journal of Photochemistry and Photobiology B: Biology     Hybrid Journal   (Followers: 3)
Journal of Physiobiochemical Metabolism     Hybrid Journal   (Followers: 1)
Journal of Physiology and Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Plant Biochemistry and Biotechnology     Hybrid Journal   (Followers: 5)
Journal of Steroid Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Journal of Virology & Antiviral Research     Hybrid Journal   (Followers: 4)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 7)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Lab on a Chip     Full-text available via subscription   (Followers: 34)
Marine Chemistry     Hybrid Journal   (Followers: 6)
Methods in Enzymology     Full-text available via subscription   (Followers: 11)
Molecular and Biochemical Parasitology     Hybrid Journal   (Followers: 2)
Molecular and Cellular Biochemistry     Hybrid Journal   (Followers: 4)
Molecular Aspects of Medicine     Hybrid Journal   (Followers: 4)
Molecular Informatics     Hybrid Journal   (Followers: 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: 5)
Natural Products and Bioprospecting     Open Access   (Followers: 3)
Nature Chemical Biology     Full-text available via subscription   (Followers: 70)
Nature Communications     Open Access   (Followers: 131)
Neurosignals     Open Access  
Novelty in Biomedicine     Open Access  
Ocean Acidification     Open Access   (Followers: 3)
Organic & Biomolecular Chemistry     Full-text available via subscription   (Followers: 87)
Peptidomics     Open Access  
Pesticide Biochemistry and Physiology     Hybrid Journal   (Followers: 4)
Pflugers Archiv European Journal of Physiology     Hybrid Journal   (Followers: 3)
Pharmaceutical Bioprocessing     Full-text available via subscription   (Followers: 1)
Pharmacognosy Magazine     Open Access   (Followers: 2)

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.478]   [H-I: 138]   [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  [3040 journals]
  • Time resolved calorimetry of photo-induced folding in horse heart
           cytochrome c at high pH
    • Authors: Tarah A. Word; Randy W. Larsen
      Pages: 10 - 14
      Abstract: Publication date: 1 February 2017
      Source:Archives of Biochemistry and Biophysics, Volume 615
      Author(s): Tarah A. Word, Randy W. Larsen
      Here the molar volume and enthalpy changes associated with the early events in the folding of ferrocytochrome c (Cc) at high pH have been examined using time resolved photoacoustic calorimetry (PAC). The data reveal an overall volume change of 1.3 ± 0.3 mL mol−1 and an enthalpy change of 13 ± 7 kcal mol −1 occurring subsequent to photodissociation of the unfolded CO bound Cc species in <∼20 ns. Two additional kinetic phases are observed that are associated with non-native His binding (ΔH and ΔV of 2 ± 4 kcal mol−1 and -0.5 mL mol−1, τ ∼ 2.5 μs ) and Met binding (ΔH and ΔV -0.4 ± 2 kcal mol−1 and -0.1 ± 0.1 mL mol−1, τ∼ 660 ns). Considering only protein conformational changes (excluding volume and enthalpies associated with heme ligation events) the initial conformational event exhibits a ΔH and ΔV of 6 ± 3 kcal mol−1 and -3±0.1 mL mol−1, respectively, that are attributed to a small contraction of the unfolded protein. The corresponding enthalpy associated with both native and non-native ligand binding are found to be −5±4 kcal mol−1 (Fe-Met) and +20 ± 4 kcal mol−1 (Fe-His) with the change in volume for both phases being essential negligible. This would indicate that non-native ligand binding likely occurs from an already collapsed conformation.
      Graphical abstract image

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/
      Issue No: Vol. 615 (2017)
  • The self-sufficient CYP102 family enzyme, Krac9955, from Ktedonobacter
           racemifer DSM44963 acts as an alkyl- and alkyloxy-benzoic acid hydroxylase
    • Authors: Natasha K. Maddigan; Stephen G. Bell
      Pages: 15 - 21
      Abstract: Publication date: 1 February 2017
      Source:Archives of Biochemistry and Biophysics, Volume 615
      Author(s): Natasha K. Maddigan, Stephen G. Bell
      A self-sufficient CYP102 family encoding gene (Krac_9955) has been identified from the bacterium Ktedonobacter racemifer DSM44963 which belongs to the Chloroflexi phylum. The characterisation of the substrate range of this enzyme was hampered by low levels of production using E. coli. The yield and purity of the Krac9555 enzyme was improved using a codon optimised gene, the introduction of a tag and modification of the purification protocol. The heme domain was isolated and in vitro analysis of substrate binding and turnover was performed. Krac9955 was found to preferentially bind alkyl- and alkyloxy-benzoic acids (≥95% high spin, K d  < 3 μM) over saturated and unsaturated fatty acids. Unusually for a self-sufficient CYP102 family member Krac9955 showed low levels of NAD(P)H oxidation activity for all the substrates tested though product formation was observed for many. For nearly all substrates the preferred site of hydroxylation of Krac9955 was eight carbons away from the carboxylate group with certain reactions proceeding at ≥ 90% selectivity. Krac9955 differs from CYP102A1 (P450Bm3), and is the first self-sufficient member of the CYP102 family of P450 enzymes which is not optimised for fast fatty acid hydroxylation close to the ω-terminus.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/
      Issue No: Vol. 615 (2017)
  • The regulation of the pentose phosphate pathway: Remember Krebs
    • Authors: Juan Ignacio Ramos-Martinez
      Pages: 50 - 52
      Abstract: Publication date: 15 January 2017
      Source:Archives of Biochemistry and Biophysics, Volume 614
      Author(s): Juan Ignacio Ramos-Martinez
      The changes in gene expression and posttranslational modifications of enzymes are comprised in the concept of “coarse control” of the oxidative phase of the pentose phosphate pathway. However, these changes are slow in its implementation. The defensive mechanism against oxidative stress requires a most rapid response, impossible to achieve with coarse regulation systems. Recently, it has been suggested that a quick acceleration mechanism of G6PD activity could be produced by the reduction of NADPH-inhibition of G6PD. The hypothesis opens new ways on possible mechanisms for rapid modulation that could be in accordance with results obtained in the 70s by Krebs. These results seemed outdated in view of the subsequent research. However, they deserve to be re-assessed at present.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/
      Issue No: Vol. 614 (2017)
  • Introduction for the Special Issue on the Chemistry of Redox Signaling
    • Authors: Henry Jay Forman; Willem H. Koppenol
      Abstract: Publication date: Available online 11 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Henry Jay Forman, Willem H. Koppenol

      PubDate: 2017-01-15T17:06:57Z
      DOI: 10.1016/
  • Altered myocyte contractility and calcium homeostasis in alpha-myosin
           heavy chain point mutations linked to familial dilated cardiomyopathy
    • Authors: Matthew Klos; Lakshmi Mundada; Indroneal Banerjee; Sherry Morgenstern; Stephanie Myers; Michael Leone; Mark Kleid; Todd Herron; Eric Devaney
      Abstract: Publication date: Available online 11 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Matthew Klos, Lakshmi Mundada, Indroneal Banerjee, Sherry Morgenstern, Stephanie Myers, Michael Leone, Mark Kleid, Todd Herron, Eric Devaney
      Mutations in the human cardiac motor protein beta-myosin heavy chain (βMHC) have been long recognized as a cause of familial hypertrophic cardiomyopathy. Recently, mutations (P830L and A1004S) in the less abundant but faster isoform alpha-myosin heavy chain (αMHC) have been linked to dilated cardiomyopathy (DCM). In this study, we sought to determine the cellular contractile phenotype associated with these point mutations. Ventricular myocytes were isolated from 2 month male Sprague Dawley rats. Cells were cultured in M199 media and infected with recombinant adenovirus containing the P830L or the A1004S mutant human αMHC at a MOI of 500 for 18 h. Uninfected cells (UI), human βMHC (MOI 500, 18 h), and human αMHC (MOI 500, 18 h) were used as controls. Cells were loaded with fura-2 (1 μM, 15 min) after 48 h. Sarcomere shortening and calcium transients were recorded in CO2 buffered M199 media (36°±1 C) with and without 10 nM isoproterenol (Iso). The A1004S mutation resulted in decreased peak sarcomere shortening while P830L demonstrated near normal shortening kinetics at baseline. In the presence of Iso, the A1004S sarcomere shortening was identical to the βMHC shortening while the P830L was identical to the αMHC control. All experimental groups had identical calcium transients. Despite a shared association with DCM, the P830L and A1004S αMHC mutations alter myocyte contractility in completely different ways while at the same preserving peak intracellular calcium.

      PubDate: 2017-01-15T17:06:57Z
      DOI: 10.1016/
  • CFTR impairment upregulates c-Src activity through IL-1β autocrine
    • Authors: María Macarena Massip-Copiz; Mariángeles Clauzure; Ángel Gabriel Valdivieso; Tomás Antonio Santa-Coloma
      Abstract: Publication date: Available online 11 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): María Macarena Massip-Copiz, Mariángeles Clauzure, Ángel Gabriel Valdivieso, Tomás Antonio Santa-Coloma
      Cystic Fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Previously, we found several genes showing a differential expression in CFDE cells (epithelial cells derived from a CF patient). One corresponded to c-Src; its expression and activity was found increased in CFDE cells, acting as a signaling molecule between the CFTR activity and MUC1 overexpression. Here we report that bronchial IB3-1 cells (CF cells) also showed increased c-Src activity compared to ‘CFTR-corrected’ S9 cells. In addition, three different Caco-2 cell lines, each stably transfected with a different CFTR-specific shRNAs, displayed increased c-Src activity. The IL-1β receptor antagonist IL1RN reduced the c-Src activity of Caco-2/pRS26 cells (expressing a CFTR-specific shRNA). In addition, increased mitochondrial and cellular ROS levels were detected in Caco-2/pRS26 cells. ROS levels were partially reduced by incubation with PP2 (c-Src inhibitor) or IL1RN, and further reduced by using the NOX1/4 inhibitor GKT137831. Thus, IL-1β→c-Src and IL-1β→NOX signaling pathways appear to be responsible for the production of cellular and mitochondrial ROS in CFTR-KD cells. In conclusion, IL-1β constitutes a new step in the CFTR signaling pathway, located upstream of c-Src, which is stimulated in cells with impaired CFTR activity.

      PubDate: 2017-01-15T17:06:57Z
      DOI: 10.1016/
  • Cytokine IL-10, activators of PI3-kinase, agonists of α-2 adrenoreceptor
           and antioxidants prevent ischemia-induced cell death in rat hippocampal
    • Authors: Egor A. Turovsky; Maria V. Turovskaya; Sergei G. Gaidin; Valery P. Zinchenko
      Abstract: Publication date: Available online 4 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Egor A. Turovsky, Maria V. Turovskaya, Sergei G. Gaidin, Valery P. Zinchenko
      In the present work we compared the protective effect of anti-inflammatory cytokine IL-10 with the action of a PI3-kinase selective activator 740Y-P, selective agonists of alpha-2 adrenoreceptor, guanfacine and UK-14,304, and compounds having antioxidant effect: recombinant human peroxiredoxin 6 and B27, in hippocampal cell culture during OGD (ischemia-like conditions). It has been shown that the response of cells to OGD in the control includes two phases. The first phase was accompanied by an increase in the frequency of spontaneous synchronous Ca2+-oscillations (SSCO) in neurons and Ca2+-pulse in astrocytes. Spontaneous Ca2+ events in astrocytes during ischemia in control experiments disappeared. The second phase started after a few minutes of OGD and looked like a sharp/avalanche, global synchronic (within 20 s) increase in [Ca2+]i in many cells. Within 1 h after OGD, a mass death of cells, primarily astrocytes, was observed. To study the protective action of the compounds, cells were incubated in the presence of the neuroprotective agents for 10–40 min or 24 h before ischemia. All the neuroprotective agents delayed a global [Ca2+]i increase during OGD or completely inhibited this process and increased cell survival.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/
  • The key residue within the second extracellular loop of human EP3 involved
           in selectively turning down PGE2-and retaining PGE1-mediated signaling in
           live cells
    • Authors: Hironari Akasaka; Natasha Thaliachery; Xianghai Zheng; Marissa Blumenthal; Sameer Nikhar; Emma E. Murdoch; Qinglan Ling; Ke-He Ruan
      Abstract: Publication date: Available online 5 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hironari Akasaka, Natasha Thaliachery, Xianghai Zheng, Marissa Blumenthal, Sameer Nikhar, Emma E. Murdoch, Qinglan Ling, Ke-He Ruan
      Key residues and binding mechanisms of PGE1 and PGE2 on prostanoid receptors are poorly understood due to the lack of X-ray structures for the receptors. We constructed a human EP3 (hEP3) model through integrative homology modeling using the X-ray structure of the β2-adrenergic receptor transmembrane domain and NMR structures of the thromboxane A2 receptor extracellular loops. PGE1 and PGE2 docking into the hEP3 model showed differing configurations within the extracellular ligand recognition site. While PGE2 could form possible binding contact with S211, PGE1 is unable to form similar contacts. Therefore, S211 could be the critical residue for PGE2 recognition, but is not a significant for PGE1. This prediction was confirmed using HEK293 cells transfected with S211L cDNA. The S211L cells lost PGE2 binding and signaling. Interestingly, the S211L cells retained PGE1-mediated signaling. It indicates that S211 within the second extracellular loop is a key residue involved in turning down PGE2 signaling. Our study provided information that S211L within EP3 is the key residue to distinguish PGE1 and PGE2 binding to mediate diverse biological functions at the initial recognition step. The S211L mutant could be used as a model for studying the binding mechanism and signaling pathway specifically mediated by PGE1.
      Graphical abstract image

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/
  • Vitamin D supplementation inhibits oxidative stress and upregulate
           SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in
           adipose tissue of high fat diet-fed diabetic mice
    • Authors: Prasenjit Manna; Arunkumar E. Achari; Sushil K. Jain
      Abstract: Publication date: Available online 4 January 2017
      Source:Archives of Biochemistry and Biophysics
      Author(s): Prasenjit Manna, Arunkumar E. Achari, Sushil K. Jain
      This study examined the hypothesis that vitamin-D prevents oxidative stress and upregulates glucose metabolism via activating insulin-independent signaling molecules in 3T3-L1 adipocytes and in high fat diet (HFD)-fed mice. To investigate the mechanism 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (1,25-dihydroxyvitamin D3) (0–50 nM). Results showed that 1,25(OH)2D3 supplementation decreased NOX4 expression, ROS production, NF-κB phosphorylation, and increased the expression of Nrf2 and Trx in HG-treated cells. 1,25(OH)2D3 supplementation upregulated SIRT1 expression and AMPK phosphorylation and stimulated the IRS1/PI3K/PIP3/AKT/PKCζ signaling cascade, GLUT4 expression, and glucose uptake in HG-treated adipocytes. The effect of 1,25(OH)2D3 on the phosphorylation of both AMPK and IRS1, GLUT4 expression, and glucose uptake was significantly inhibited in SIRT1-knockdown adipocytes. This suggests the role of insulin-independent signaling molecules (SIRT1, AMPK) in mediating the effect of 1,25(OH)2D3 on the signaling cascade of glucose uptake. In addition, cholecalciferol supplementation significantly upregulated pAMPK, SIRT-1 and GLUT-4 levels in adipose tissue of mice fed with HFD. This study demonstrates a novel molecular mechanism by which vitamin-D can prevent oxidative stress and upregulates glucose uptake via SIRT1/AMPK/IRS1/GLUT4 cascade in HG-treated adipocytes and in adipose tissue of HFD diabetic mice.

      PubDate: 2017-01-07T16:29:04Z
      DOI: 10.1016/
  • Structural and functional studies of the Leishmania braziliensis
           mitochondrial Hsp70: Similarities and dissimilarities to human orthologues
    • Authors: Paulo R. Dores-Silva; Letícia S. Nishimura; Vanessa T.R. Kiraly; Júlio C. Borges
      Pages: 43 - 52
      Abstract: Publication date: 1 January 2017
      Source:Archives of Biochemistry and Biophysics, Volume 613
      Author(s): Paulo R. Dores-Silva, Letícia S. Nishimura, Vanessa T.R. Kiraly, Júlio C. Borges
      Heat shock protein 70 kDa (Hsp70) is a conserved molecular chaperone family involved in several functions related to protein homeostasis. In eukaryotes, Hsp70 homologues are found in all cell compartments. The mitochondrial Hsp70 isoform (mtHsp70) is involved in import of mitochondrial matrix proteins as well as their folding and maturation. Moreover, mtHsp70 has the propensity to self-aggregate, and it depends on the action of the co-chaperone Hsp70-escort protein 1 (Hep1) to be produced functional. Here, we analyze the solution structure and function of mtHsp70 of Leishmania braziliensis (LbmtHsp70). This recombinant protein was obtained folded, in the monomeric state and it has an elongated shape. We observed that LbmtHsp70 suffers thermal aggregation that depends on the protein concentration and is composed of domains with different thermal stabilities. LbmtHsp70 interacted with adenosine nucleotides with a thermodynamic signature different from those reported for human orthologues and interacted, driven by both enthalpy and entropy, with L. braziliensis Hep1 (LbHep1) with a nanomolar dissociation constant. Moreover, LbHep1 stimulated the LbmtHsp70 ATPase activity. Since little is known about mitochondrial Hsp70, particularly in protozoa, we believe that our data are of interest for understanding protozoan Hsp70 machinery.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 613 (2016)
  • Cyclophilin D over-expression increases mitochondrial complex III activity
           and accelerates supercomplex formation
    • Authors: Julie C. Etzler; Mariana Bollo; Deborah Holstein; Janice Jianhong Deng; Viviana Perez; Da-ting Lin; Arlan Richardson; Yidong Bai; James D. Lechleiter
      Pages: 61 - 68
      Abstract: Publication date: 1 January 2017
      Source:Archives of Biochemistry and Biophysics, Volume 613
      Author(s): Julie C. Etzler, Mariana Bollo, Deborah Holstein, Janice Jianhong Deng, Viviana Perez, Da-ting Lin, Arlan Richardson, Yidong Bai, James D. Lechleiter
      Cyclophilin D (CyPD), a mitochondrial matrix protein, has been widely studied for its role in mitochondrial-mediated cell death. Unexpectedly, we previously discovered that overexpression of CyPD in a stable cell line, increased mitochondrial membrane potentials and enhanced cell survival under conditions of oxidative stress. Here, we investigated the underlying mechanisms responsible for these findings. Spectrophotometric measurements in isolated mitochondria revealed that overexpression of CyPD in HEK293 cells increased respiratory chain activity, but only for Complex III (CIII). Acute treatment of mitochondria with the immumosupressant cyclosporine A did not affect CIII activity. Expression levels of the CIII subunits cytochrome b and Rieske-FeS were elevated in HEK293 cells overexpressing CyPD. However, CIII activity was still significantly higher compared to control mitochondria, even when normalized by protein expression. Blue native gel electrophoresis and Western blot assays revealed a molecular interaction of CyPD with CIII and increased levels of supercomplexes in mitochondrial protein extracts. Radiolabeled protein synthesis in mitochondria showed that CIII assembly and formation of supercomplexes containing CIII were significantly faster when CyPD was overexpressed. Taken together, these data indicate that CyPD regulates mitochondrial metabolism, and likely cell survival, by promoting more efficient electrons flow through the respiratory chain via increased supercomplex formation.

      PubDate: 2016-12-08T01:10:59Z
      DOI: 10.1016/
      Issue No: Vol. 613 (2016)
  • Crystal structures of the CO and NOBound DosS GAF-A domain and
           implications for DosS signaling in Mycobacterium tuberculosis
    • Authors: Yarrow Madrona; Christopher A. Waddling; Paul R. Ortiz de Montellano
      Pages: 1 - 8
      Abstract: Publication date: 15 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 612
      Author(s): Yarrow Madrona, Christopher A. Waddling, Paul R. Ortiz de Montellano
      DosS is a sensor in Mycobacterium tuberculosis that differentially responds to O2, NO, and CO, as well as to changes in the redox state of the prosthetic heme iron atom. The ferrous protein and its Fe(II)NO and Fe(II)CO complexes undergo autophosphorylation and subsequently transfer the phosphate group to DosR, a nuclear factor, to activate it. In contrast, autophosphorylation is negligible with the ferric protein and the Fe(II)O2 complex. To clarify the basis for this differential response to gases, we have determined the crystal structures of the NO and COcomplexes of the DosS GAF-A domain, which contains the heme to which the gases bind. Comparison of these crystal structures with those reported for the phosphorylation-inactive ferric GAF-A domain suggest that the GAF-A domain is in a dynamic equilibrium between active and inactive states, and that the position of Glu87 in the heme cavity, which depends on the which gas is bound, acts as a modulator of the equilibrium, and therefore of catalytic activity.
      Graphical abstract image

      PubDate: 2016-10-13T16:34:04Z
      DOI: 10.1016/
      Issue No: Vol. 612 (2016)
  • Insight into the impact of two structural calcium ions on the properties
           of Pleurotus eryngii versatile ligninolytic peroxidase
    • Authors: Yu Gao; Lanyan Zheng; Jian-Jun Li; Yuguang Du
      Pages: 9 - 16
      Abstract: Publication date: Available online 5 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yu Gao, Lanyan Zheng, Jian-Jun Li, Yuguang du
      Two structural Ca2+ (proximal and distal) is known to be important for ligninolytic peroxidases. However, few studies toward impact of residues involved in two Ca2+ on properties of ligninolytic peroxidases have been done, especially the proximal one. In this study, mutants of nine residues involved in liganding two Ca2+ of Pleurotus eryngii versatile peroxidase (VP) were investigated. Most mutants almost completely lost activities, except the mutants of proximal Ca2+ - S170A and V192T. In comparison with WT (wild type), optimal pH values of S170A, S170D, and V192T shifted from pH 3.0 to pH 3.5. The order of thermal and pH stabilities of WT, V192T, S170A, and S170D is similar to that of their specific activities: WT > V192T > S170A > S170D. The CD (circular dichroism) results of WT and several mutants indicated that mutations had some effects on secondary structures. For the first time, it was observed that the thermostability of ligninolytic peroxidases is related with proximal Ca2+ too, and the mutant containing distal Ca2+ only was obtained. Our results clearly demonstrated that enzymatic activities, pH and thermal stabilities, Ca2+content, and secondary structures of VP have close relationship with the residues involved in two structural Ca2+.

      PubDate: 2016-10-06T16:07:59Z
      DOI: 10.1016/
      Issue No: Vol. 612 (2016)
  • Insights into kinetic mechanism of Janus kinase 3 and its inhibition by
    • Authors: Mohammad Hekmatnejad; Sara Conwell; Stephen M. Lok; Alan Kutach; David Shaw; Eric Fang; David C. Swinney
      Pages: 22 - 34
      Abstract: Publication date: 15 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 612
      Author(s): Mohammad Hekmatnejad, Sara Conwell, Stephen M. Lok, Alan Kutach, David Shaw, Eric Fang, David C. Swinney
      JAK3 kinase plays a critical role in several cytokine signaling pathways involved in immune cell development and function. The studies presented in this report were undertaken to elucidate the kinetic mechanism of the JAK3 kinase domain, investigate the role of activation loop phosphorylation in regulating its catalytic activity, and examine its inhibition by the anti-rheumatoid arthritis drug, tofacitinib. Phosphorylation of two Tyr residues in JAK3's activation loop has been reported to impact its kinase activity. The recombinant JAK3 kinase domain used in our studies was heterogeneous in its activation loop phosphorylation, with the non-phosphorylated protein being the dominant species. Kinetic analysis revealed similar kinetic parameters for the heterogeneously phosphorylated JAK3, JAK3 mono-phosphorylated on Tyr 980, and the activation loop mutant YY980/981FF. Bisubstrate and product inhibition kinetic results were consistent with both sequential random and sequential ordered kinetic mechanisms. Solvent viscosometric experiments showed perturbation of k cat, suggesting the phosphoryl transfer step is not likely rate limiting. This was supported by results from quench-flow experiments, where a rapid burst of product formation was observed. Kinetic analysis of JAK3 inhibition by tofacitinib indicated inhibition is time dependent, characterized by on- and off-rate constants of 1.4 ± 0.1 μM−1s−1 and 0.0016 ± 0.0005 s−1, respectively.

      PubDate: 2016-10-19T12:26:14Z
      DOI: 10.1016/
      Issue No: Vol. 612 (2016)
  • Steady-state kinetic studies reveal that the anti-cancer target
           Ubiquitin-Specific Protease 17 (USP17) is a highly efficient
           deubiquitinating enzyme
    • Authors: Nicole M. Hjortland; Andrew D. Mesecar
      Pages: 35 - 45
      Abstract: Publication date: Available online 15 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Nicole M. Hjortland, Andrew D. Mesecar
      USP17 is a deubiquitinating enzyme that is upregulated in numerous cancers and therefore a drug target. We developed a robust expression, purification, and assay system for USP17 enabling its enzymatic and structural characterization. USP17 was expressed in E. coli as inclusion bodies and then solubilized, refolded, and purified using affinity and size-exclusion chromatography. Milligram quantities of pure USP17 can be produced that is catalytically more efficient (kcat/Km = 1500 (x103) M−1 sec−1) than other human USPs studied to date. Analytical size-exclusion chromatography, analytical ultracentrifugation, and dynamic light scattering studies suggest that the quaternary structure of USP17 is a monomer. Steady-state kinetic studies show that USP17 efficiently hydrolyzes both ubiquitin-AMC (kcat = 1.5 sec−1 and Km = 1.0 μM) and ubiquitin-rhodamine110 (kcat = 1.8 sec−1 and Km = 2.0 μM) substrates. Ubiquitin chain cleavage assays reveal that USP17 efficiently cleaves di-ubiquitin chains with Lys11, Lys33, Lys48 and Lys63 linkages and tetra-ubiquitin chains with Lys11, Lys48 and Lys63 linkages but is inefficient in cleaving di-ubiquitin chains with Lys6, Lys27, or Lys29 linkages or linear ubiquitin chains. The substrate specificity of USP17 is most similar to that of USP1, where both USPs display higher specificity than other characterized members of the USP family.
      Graphical abstract image

      PubDate: 2016-10-19T12:26:14Z
      DOI: 10.1016/
      Issue No: Vol. 612 (2016)
  • Corrigendum to “CD147 induces up-regulation of vascular endothelial
           growth factor in U937-derived foam cells through PI3K/AKT pathway”
           [Arch. Biochem. Biophys. 609 (2016) 31–38]
    • Authors: JiaXin Zong; YunTian Li; DaYong Du; Yang Liu; YongJun Yin
      First page: 120
      Abstract: Publication date: 15 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 612
      Author(s): JiaXin Zong, YunTian Li, DaYong Du, Yang Liu, YongJun Yin

      PubDate: 2016-11-23T15:43:39Z
      DOI: 10.1016/
      Issue No: Vol. 612 (2016)
  • Editorial: The cutting edge of zinc biology
    • Authors: Taiho Kambe; Toshiyuki Fukada; Shinya Toyokuni
      Pages: 1 - 2
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Taiho Kambe, Toshiyuki Fukada, Shinya Toyokuni

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • The biological inorganic chemistry of zinc ions
    • Authors: Artur Krężel; Wolfgang Maret
      Pages: 3 - 19
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      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: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Techniques for measuring cellular zinc
    • Authors: Margaret C. Carpenter; Maria N. Lo; Amy E. Palmer
      Pages: 20 - 29
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Margaret C. Carpenter, Maria N. Lo, Amy E. Palmer
      The development and improvement of fluorescent Zn2+ sensors and Zn2+ imaging techniques have increased our insight into this biologically important ion. Application of these tools has identified an intracellular labile Zn2+ pool and cultivated further interest in defining the distribution and dynamics of labile Zn2+. The study of Zn2+ in live cells in real time using sensors is a powerful way to answer complex biological questions. In this review, we highlight newly engineered Zn2+ sensors, methods to test whether the sensors are accessing labile Zn2+, and recent studies that point to the challenges of using such sensors. Elemental mapping techniques can complement and strengthen data collected with sensors. Both mass spectrometry-based and X-ray fluorescence-based techniques yield highly specific, sensitive, and spatially resolved snapshots of metal distribution in cells. The study of Zn2+ has already led to new insight into all phases of life from fertilization of the egg to life-threatening cancers. In order to continue building new knowledge about Zn2+ biology it remains important to critically assess the available toolset for this endeavor.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Zinc sensing and regulation in yeast model systems
    • Authors: Stevin Wilson; Amanda J. Bird
      Pages: 30 - 36
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Stevin Wilson, Amanda J. Bird
      The Zap1 transcription factor of Saccharomyces cerevisiae and the Loz1 transcription factor of Schizosaccharomyces pombe both play a central role in zinc homeostasis by controlling the expression of genes necessary for zinc metabolism. Zap1 activates gene expression when cells are limited for zinc, while Loz1 is required for gene repression when zinc is in excess. In this review we highlight what is known about the underlying mechanisms by which these factors are regulated by zinc, and how transcriptional activation and repression in eukaryotic cells can be finely tuned according to intracellular zinc availability.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Activation of zinc-requiring ectoenzymes by ZnT transporters during the
           secretory process: Biochemical and molecular aspects
    • Authors: Taiho Kambe; Taka-aki Takeda; Yukina Nishito
      Pages: 37 - 42
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Taiho Kambe, Taka-aki Takeda, Yukina Nishito
      In humans, about 1000 enzymes are estimated to bind zinc. In most of these enzymes, zinc is present at the active site; thus, these enzymes are functional as “zinc-requiring enzymes”. Of these zinc-requiring enzymes, zinc-requiring ectoenzymes (defined as secretory, membrane-bound, and organelle-resident enzymes) have received much attention because of their important physiological functions, involvement in a number of diseases, and potential applications as therapeutic targets for diseases. Zinc-requiring ectoenzymes may become active by coordinating zinc at their active site during the secretory process, which requires elaborate control of zinc mobilization from the extracellular milieu to the cytosol and then lumen in the early secretory pathway. Therefore, zinc transporters should properly maintain the process at systemic, cellular, and subcellular levels by mobilizing zinc across biological membranes. However, few studies have examined the mechanisms underlying this process. In this review, current knowledge of the activation process of zinc-requiring ectoenzymes by ZnT zinc transporters in the early secretory pathway is briefly reviewed at the molecular level, with a focus on tissue-nonspecific alkaline phosphatase. Moreover, we also discuss whether zinc-chaperone proteins function during the activation of these enzymes.
      Graphical abstract image

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Zinc transporters and signaling in physiology and pathogenesis
    • Authors: Shintaro Hojyo; Toshiyuki Fukada
      Pages: 43 - 50
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Shintaro Hojyo, Toshiyuki Fukada
      Zinc (Zn) is an essential trace element that is vital in a wide range of cellular machineries because of its effect on the expression and activity of various transcription factors and enzymes. Zn deficiency disturbs Zn homeostasis and has pathogenic consequences, including growth retardation and immune impairment in mammals. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the distribution, storage, and intracellular and extracellular concentration of Zn. Recent reverse-genetic approaches using Zn transporter–deficient mice have revealed the physiological functions of specific Zn signaling axes (each formed by Zn and a Zn transporter) in various biological programs. In this review, we describe recent discoveries about the role of Zn transporters which facilitate cellular signaling through Zn uptake in physiology and pathogenesis, with particular focus on the influence of Zn signaling in systemic growth and immunity.
      Graphical abstract image

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Zinc and infant nutrition
    • Authors: M. Leigh Ackland; Agnes A. Michalczyk
      Pages: 51 - 57
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): M. Leigh Ackland, Agnes A. Michalczyk
      Zinc is essential for a wide variety of cellular processes in all cells. It is a critical dietary nutrient, particularly in the early stages of life. In the early neonatal period, adequate sources of zinc can be obtained from breast milk. In rare circumstances, the mammary gland produces zinc deficient milk that is potentially lethal for exclusively breast-fed infants. This can be overcome by zinc supplementation to the infant. Alterations to key zinc transporters provide insights into the mechanisms of cellular zinc homeostasis. The bioavailability of zinc in food depends on the presence of constituents that may complex zinc. In many countries, zinc deficiency is a major health issue due to poor nourishment. Young children are particularly affected. Zinc deficiency can impair immune function and contributes to the global burden of infectious diseases including diarrhoea, pneumonia and malaria. Furthermore, zinc deficiency may extend its influence across generations by inducing epigenetic effects that alter the expression of genes. This review discusses the significance of adequate zinc nutrition in infants, factors that influence zinc nutrition, the consequences of zinc deficiency, including its contribution to the global burden of disease, and addresses some of the knowledge gaps in zinc biology.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Zinc and immunity: An essential interrelation
    • Authors: Maria Maares; Hajo Haase
      Pages: 58 - 65
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Maria Maares, Hajo Haase
      The significance of the essential trace element zinc for immune function has been known for several decades. Zinc deficiency affects immune cells, resulting in altered host defense, increased risk of inflammation, and even death. The micronutrient zinc is important for maintenance and development of immune cells of both the innate and adaptive immune system. A disrupted zinc homeostasis affects these cells, leading to impaired formation, activation, and maturation of lymphocytes, disturbed intercellular communication via cytokines, and weakened innate host defense via phagocytosis and oxidative burst. This review outlines the connection between zinc and immunity by giving a survey on the major roles of zinc in immune cell function, and their potential consequences in vivo.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Immunological orchestration of zinc homeostasis: The battle between host
           mechanisms and pathogen defenses
    • Authors: Kavitha Subramanian Vignesh; George S. Deepe
      Pages: 66 - 78
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Kavitha Subramanian Vignesh, George S. Deepe
      The importance of Zn ions (Zn) in regulating development and functions of the immune system is well established. However, recent years have witnessed a surge in our knowledge of how immune cells choreograph Zn regulatory mechanisms to combat the persistence of pathogenic microbes. Myeloid and lymphoid populations manipulate intracellular and extracellular Zn metabolism via Zn binding proteins and transporters in response to immunological signals and infection. Rapid as well as delayed changes in readily exchangeable Zn, also known as free Zn and the Zn proteome are crucial in determining activation of immune cells, cytokine responses, signaling and nutritional immunity. Recent studies have unearthed distinctive Zn modulatory mechanisms employed by specialized immune cells and necessitate an understanding of the Zn handling behavior in immune responses to infection. The focus of this review, therefore, stems from novel revelations of Zn intoxication, sequestration and signaling roles deployed by different immune cells, with an emphasis on innate immunity, to challenge microbial parasitization and cope with pathogen insult.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Zinc and diabetes
    • Authors: Pauline Chabosseau; Guy A. Rutter
      Pages: 79 - 85
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Pauline Chabosseau, Guy A. Rutter
      Zn2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet β and α cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn2+ ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Molecular regulation of lactation: The complex and requisite roles for
    • Authors: Sooyeon Lee; Shannon L. Kelleher
      Pages: 86 - 92
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Sooyeon Lee, Shannon L. Kelleher
      Lactation provides many health benefits to the nursing infant and breastfeeding mother. In order to successfully breastfeed, the mammary gland must expand and differentiate to activate numerous processes that regulate milk production and secretion. This involves a complex series of molecular, biochemical and cellular events driven largely by lactogenic hormones. Recent advances implicate zinc as a critical modulator of mammary gland function. Here, we provide an overview of our current understanding of the role and regulation of zinc in promoting proliferation, differentiation and secretion in the mammary gland during lactation, and highlight critical gaps in knowledge.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Insight into cognitive decline from Zn2+ dynamics through extracellular
           signaling of glutamate and glucocorticoids
    • Authors: Atsushi Takeda; Hanuna Tamano
      Pages: 93 - 99
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      Author(s): Atsushi Takeda, Hanuna Tamano
      Glutamatergic neuron activity and/or the modification of the activity with glucocorticoids are closely linked to synaptic Zn2+ dynamics as well as synaptic Ca2+ dynamics. The dynamic crosstalk of synaptic Zn2+ signaling to intracellular Ca2+ signaling via calcium channels is involved in synaptic plasticity such as long-term potentiation (LTP) and cognitive activity. The influx of extracellular Zn2+ into postsynaptic neurons, which is closely linked to glutamate signaling in the synaptic cleft, is critical for cognitive activity. However, excess intracellular Zn2+ signaling induced by excess glutamatergic neuron activity is involved in not only cognitive decline in neurological disorders but also stress-induced cognitive decline. On the other hand, it has been recognized that excess Ca2+ influx into postsynaptic neurons induces neuronal death, while the involvement of excess intracellular Ca2+ signaling in cognitive decline is poorly understood. Understanding of synaptic Zn2+ dynamics, which are modified by glutamate and glucocorticoid signaling, may be meaningful to prevent Zn2+-mediated cognitive decline. This paper summarizes the current knowledge on Zn2+ dynamics under changing synaptic environment and its impact on cognitive decline.

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • A comprehensive review of the role of zinc in normal prostate function and
           metabolism; and its implications in prostate cancer
    • Authors: Leslie C. Costello; Renty B. Franklin
      Pages: 100 - 112
      Abstract: Publication date: 1 December 2016
      Source:Archives of Biochemistry and Biophysics, Volume 611
      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 levels of citrate, which is achieved by the high cellular zinc level effects 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: 2016-11-16T15:31:43Z
      DOI: 10.1016/
      Issue No: Vol. 611 (2016)
  • Penicillin acylase and O-Acyl hydroxamates: Two acyl-enzymes, one leading
           to hydrolysis, the other to inactivation
    • Authors: S.A. Adediran; R.F. Pratt
      Abstract: Publication date: Available online 27 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): S.A. Adediran, R.F. Pratt
      O-Aryloxycarbonyl hydroxamates have previously been shown to covalently inactivate serine/amine amidohydrolases such as class C β-lactamases and a N-terminal hydrolase, the proteasome. We report here reactions between O-aryloxycarbonyl hydroxamates and another N-terminal hydrolase, penicillin acylase. O-Aryloxycarbonyl hydroxamates, as non-symmetric carbonates, have two different leaving groups attached to the reactive central carbonyl group. We propose that these compounds can bind to the active site in either of two orientations and that either leaving group can be displaced from either orientation. In the present case we detected from kinetics experiments two distinct acyl-enzymes, one of which is subject to normal hydrolysis and the other to inactivation. Non-symmetric carbonates therefore can be very versatile enzyme inactivators.
      Graphical abstract image

      PubDate: 2016-12-29T15:56:49Z
      DOI: 10.1016/
  • Insights into the mechanism of Apoptin's exquisitely selective anti-tumor
           action from atomic level characterization of its conformation and dynamics
    • Authors: Santiago Ruiz-Martínez; David Pantoja-Uceda; Jessica Castro; Maria Vilanova; Marc Ribó; Marta Bruix; Antoni Benito; Douglas V. Laurents
      Abstract: Publication date: Available online 27 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Santiago Ruiz-Martínez, David Pantoja-Uceda, Jessica Castro, Maria Vilanova, Marc Ribó, Marta Bruix, Antoni Benito, Douglas V. Laurents
      Apoptin is a 121 residue protein which forms large, soluble aggregates and possesses an exceptionally selectively cytotoxic action on cancer cells. In the accompanying paper, we described the design, production and initial characterization of an Apoptin truncated variant called H6-ApopΔProΔLeu. Whereas both the variant and wild type protein possess similar selective cytotoxicity against cancer cells following transfection, only the variant is cytotoxic when added externally. Remarkably, as observed by gel filtration chromatography and dynamic light scattering, H6-ApopΔProΔLeu lacks the tendency of wild type Apoptin to form large aggregates, which greatly facilitated the study of its biological properties. Here, we characterize the conformation and dynamics of H6-ApopΔProΔLeu. Using a battery of 2D, 3D and (4,2)D NMR spectra, the essentially complete 1H, 13C and 15N resonance assignments of H6-ApopΔProΔLeu were obtained. The analysis of these data shows that the variant is an intrinsically disordered protein, which lacks a preferred conformation. This conclusion is corroborated by a lack of protection against proteolytic cleavage and hydrogen/deuterium exchange. Moreover, the CD spectra are dominated by random coil contributions. Finally, 1H-15N NOE ratios are low, which indicates flexibility on the ps-ns time scale. Interestingly, H6-ApopΔProΔLeu's intrinsically disordered ensemble is not significantly altered by the redox state of its Cys residues or by Thr phosphorylation, which has been proposed to play a key role in Apoptin's selective cytotoxicity. These results serve to better comprehend Apoptin's remarkably selective anticancer action and provide a framework for the future design of improved Apoptin variants.
      Graphical abstract image

      PubDate: 2016-12-29T15:56:49Z
      DOI: 10.1016/
  • Effects of testosterone on mean arterial pressure and aquaporin (AQP)-1,
           2, 3, 4, 6 and 7 expressions in the kidney of orchidectomized, adult male
           Sprague-Dawley rats
    • Authors: Su Yi Loh; Nelli Giribabu; Khadijeh Gholami; Naguib Salleh
      Abstract: Publication date: Available online 23 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Su Yi Loh, Nelli Giribabu, Khadijeh Gholami, Naguib Salleh
      We hypothesized that higher blood pressure in males than females could be due to testosterone effects on aquaporin (AQP) expression in kidneys. Methods: Orchidectomized adult male Sprague-Dawley (SD) rats received seven days subcutaneous testosterone treatment (125 μg/kg/day or 250 μg/kg/day), with or without flutamide or finasteride. Following completion of treatment, MAP was determined in rats under anaesthesia via carotid artery cannulation. In another cohort of rats, kidneys were removed following sacrifice and AQP-1, 2, 3, 4, 6 and 7 protein and mRNA levels were determined by Western blotting and Real-time PCR respectively. Distribution of AQP subunits' protein in the nephrons were visualized by immunofluorescence. Results Testosterone caused MAP, AQP-1, 2, 4, 6 and 7 protein and mRNA levels in kidneys to increase while AQP-3 protein and mRNA levels in kidneys to decrease (p < 0.05). AQP-1 and 7 were found to be distributed in the proximal convoluted tubule (PCT) while AQP-2, 3, 4 and 6 were found to be distributed in the collecting ducts (CD). Effects of testosterone were antagonized by flutamide and finasteride. Conclusions Elevated expression of AQP-1, 2, 4, 6 and 7 under testosterone influence in kidneys could lead to increase H2O reabsorption which eventually lead to increase in blood pressure.

      PubDate: 2016-12-29T15:56:49Z
      DOI: 10.1016/
  • The long non-coding RNA NEAT1 interacted with miR-101 modulates breast
           cancer growth by targeting EZH2
    • Authors: Ke Qian; Gao Liu; Zhonghua Tang; Yibo Hu; Yu Fang; Zonglin Chen; Xundi Xu
      Abstract: Publication date: Available online 26 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ke Qian, Gao Liu, Zhonghua Tang, Yibo Hu, Yu Fang, Zonglin Chen, Xundi Xu
      Nuclear enriched abundant transcript 1 (NEAT1), an important cancer-associated long non-coding RNA (lncRNA), contributes to the development and progression of several cancers. An increased expression of NEAT1 was observed in cancers including bladder cancer, lung cancer and breast cancer (BC). However, the exact effect of NEAT1 in BC progression and the underlying molecular mechanisms are still unknown up to now. Here, we investigated the detailed role of NEAT1 in human BC cell lines and clinical tumor samples in order to validate the function of this molecule. In our research, lncRNA-NEAT1 was specifically upregulated in BC cell lines and promoted BC cell growth through targeting miR-101. Knockdown of NEAT1 inhibited the proliferation and DNA synthesis of human BC cell in vitro. In addition, the regulation of EZH2 by miR-101 was required in NEAT1 induced BC cell growth. These findings indicated that NEAT1 might suppress the tumor growth via miR-101 dependent EZH2 regulation. Taken together, our data indicated that NEAT1 might be an oncogenic lncRNA that promoted proliferation of BC and could be regarded as a therapeutic target in human BC.

      PubDate: 2016-12-29T15:56:49Z
      DOI: 10.1016/
  • Conformational status of cytochrome c upon N-homocysteinylation:
           Implications to cytochrome c release
    • Authors: Gurumayum Suraj Sharma; Laishram Rajendrakumar Singh
      Abstract: Publication date: Available online 18 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Gurumayum Suraj Sharma, Laishram Rajendrakumar Singh
      One of the proposed mechanisms of homocysteine (Hcy) toxicity is the post-translational modification of proteins by its metabolite, homocysteine thiolactone (HTL). Incubation of proteins with HTL has been shown to form covalent adducts with ε-amino group of lysine residues of protein (called N-homocysteinylation) which ultimately results in structural and functional alterations of the modified proteins. In the present study, the effects of HTL on the conformational and heme status of cytochrome c (cyt c) were investigated. Spectroscopic analyses revealed that HTL-modified cyt c undergoes certain conformational alterations leading to disturbed heme-Trp distance and packing of the apolar groups. These alterations were accompanied with the reduction of the heme moiety and activation of peroxidase-like function of cyt c, which is known to be a crucial event for initiation of the intrinsic apoptotic pathway. Further structural characterization revealed that disruption of the heme-Met80 interaction, thereby converting the hexa-coordinate cyt c to a penta-coordinate species (with a free heme ligand), was responsible for the activation of the peroxidase activity. The study provides insights for the possible role of cyt c N-homocysteinylation in eliciting its toxicity and cell death.
      Graphical abstract image

      PubDate: 2016-12-23T04:37:23Z
      DOI: 10.1016/
  • Molecular mechanisms of deregulation of the thin filament associated with
           the R167H and K168E substitutions in tropomyosin Tpm1.1
    • Authors: Yurii S. Borovikov; Nikita A. Rysev; Stanislava V. Avrova; Olga E. Karpicheva; Danuta Borys; Joanna Moraczewska
      Abstract: Publication date: Available online 9 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yurii S. Borovikov, Nikita A. Rysev, Stanislava V. Avrova, Olga E. Karpicheva, Danuta Borys, Joanna Moraczewska
      Point mutations R167H and K168E in tropomyosin Tpm1.1 (TM) disturb Ca2+-dependent regulation of the actomyosin ATPase. To understand mechanisms of this defect we studied multistep changes in mobility and spatial arrangement of tropomyosin, actin and myosin heads during the ATPase cycle in reconstituted ghost fibers using the polarized fluorescence microscopy. It was found that both mutations disturbed the mode of troponin operation in the fibers. At high Ca2+, troponin increased the fraction of actin monomers that were in the “switched on” state, but both mutant tropomyosins were shifted toward the outer actin domains, which decreased the fraction of strongly bound myosin heads throughout the ATPase cycle. At low Ca2+, the R167H-TM was located close to the outer actin domains, which reduced the number of strongly-bound myosin heads. However, under these conditions troponin increased the number of actin monomers that were switched on. The K168E-TM was displaced far to the outer actin domains and troponin binding decreased the fraction of switched on actin monomers, but the proportion of the strongly bound myosin heads was abnormally high. Thus, the mutations differently disturbed transmission of conformational changes between troponin, tropomyosin and actin, which is essential for the Са2+-dependent regulation of the thin filament.

      PubDate: 2016-12-15T01:20:47Z
      DOI: 10.1016/
  • Reduction of quinones and nitroaromatic compounds by Escherichia coli
           nitroreductase A (NfsA): Characterization of kinetics and substrate
    • Authors: Benjaminas Valiauga; Elsie M. Williams; David F. Ackerley; Narimantas Čėnas
      Abstract: Publication date: Available online 13 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Benjaminas Valiauga, Elsie M. Williams, David F. Ackerley, Narimantas Čėnas
      NfsA, a major FMN-associated nitroreductase of E. coli, reduces nitroaromatic compounds via consecutive two-electron transfers. NfsA has potential applications in the biodegradation of nitroaromatic environment pollutants, e.g. explosives, and is also of interest for the anticancer strategy gene-directed enzyme prodrug therapy. However, the catalytic mechanism of NfsA is poorly characterized. Here we examined the NADPH-dependent reduction of quinones (n = 16) and nitroaromatic compounds (n = 12) by NfsA. We confirmed a general “ping-pong” reaction scheme, and preliminary rapid reaction studies of the enzyme reduction by NADPH showed that this step is much faster than the steady-state turnover number, i.e., the enzyme turnover is limited by the oxidative half-reaction. The reactivity of nitroaromatic compounds (log k cat/K m) followed a linear dependence on their single-electron reduction potential (E 1 7), indicating a limited role for compound structure or active site flexibility in their reactivity. The reactivity of quinones was lower than that of nitroaromatics having similar E 1 7 values, except for the significantly enhanced reactivity of 2-OH-1,4-naphthoquinones, consistent with observations previously made for the group B nitroreductase of Enterobacter cloacae. We present evidence that the reduction of quinones by NfsA is most consistent with a single-step (H−) hydride transfer mechanism.

      PubDate: 2016-12-15T01:20:47Z
      DOI: 10.1016/
  • Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell
    • Authors: Aron B. Fisher
      Abstract: Publication date: Available online 6 December 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Aron B. Fisher
      Peroxiredoxin 6 represents a widely distributed group of peroxiredoxins that contain a single conserved cysteine in the protein monomer (1-cys Prdx). The cys when oxidized to the sulfenic form is reduced with glutathione (GSH) catalyzed by the π isoform of GSH-S-transferase. Three enzymatic activities of the protein have been described:1) peroxidase with H2O2, short chain hydroperoxides and phospholipid hydroperoxides as substrates; 2) phospholipase A2 (PLA2); and 3) lysophosphatidylcholine acyl transferase (LPCAT). These activities have important physiological roles in antioxidant defense, turnover of cellular phospholipids, and the generation of superoxide anion via initiation of the signaling cascade for activation of NADPH oxidase (type 2). The ability of Prdx6 to reduce peroxidized cell membrane phospholipids (peroxidase activity) and also to replace the oxidized sn-2 fatty acyl group through hydrolysis/reacylation (PLA2 and LPCAT activities) provides a complete system for the repair of peroxidized cell membranes.

      PubDate: 2016-12-08T01:10:59Z
      DOI: 10.1016/
  • Influence of sequence and lipid type on membrane perturbation by human and
           rat amyloid β-peptide (1–42)
    • Authors: Anne M. Brown; David R. Bevan
      Abstract: Publication date: Available online 21 November 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Anne M. Brown, David R. Bevan
      The hallmark characteristics of plaque formation and neuronal cell death in Alzheimer's disease (AD) are caused principally by the amyloid β-peptide (Aβ). Aβ sequence and lipid composition are essential variables to consider when elucidating the impact of biological membranes on Aβ structure and the effect of Aβ on membrane integrity. Atomistic molecular dynamics simulations testing two Aβ sequences, human and rat Aβ (HAβ and RAβ, respectively), and five lipid types were performed to assess the effect of these variables on membrane perturbation and potential link to AD phenotype differences based on differences in sequence. All metrics agree insomuch that monomeric HAβ and RAβ contribute to membrane perturbation by causing a more rigid, gel-like lipid phase. Differences between HAβ and RAβ binding on degree of membrane perturbation were based on lipid headgroup properties. Cholesterol was found to moderate the amount of perturbation caused by HAβ and RAβ in a model raft membrane. The difference in position of an arginine residue between HAβ and RAβ influenced peptide-membrane interactions and was determined to be the mediating factor in observed differences in lipid affinity and degree of membrane disruption. Overall, this work increases our understanding of the influence of sequence and lipid type on Aβ-membrane interactions and their relationship to AD.
      Graphical abstract image

      PubDate: 2016-11-23T15:43:39Z
      DOI: 10.1016/
  • Long-term inhibition of cyclophilin D results in intracellular
           translocation of calcein AM from mitochondria to lysosomes
    • Authors: Daisuke Shinohe; Asuka Kobayashi; Marina Gotoh; Kotaro Tanaka; Yoshihiro Ohta
      Abstract: Publication date: Available online 15 November 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Daisuke Shinohe, Asuka Kobayashi, Marina Gotoh, Kotaro Tanaka, Yoshihiro Ohta
      Cyclophilin D is a peptidyl-prolyl cis-trans isomerase localized in the mitochondrial matrix. Although its effects on mitochondrial characteristics have been well studied, its relation to the uptake of molecules by mitochondria remains unknown. Here, we demonstrated the effects of cyclophilin D on the intracellular translocation of calcein AM. Following addition of calcein AM to control cells or cells overexpressing wild-type cyclophilin D, calcein fluorescence was observed in mitochondria. However, long-term inhibition of cyclophilin D in these cells altered the localization of calcein fluorescence from mitochondria to lysosomes without changing mitochondrial esterase activity. In addition, depletion of glucose from the medium recovered calcein localization from lysosomes to mitochondria. This is the first demonstration of the effects of cyclophilin D on the intracellular translocation of molecules other than proteins and suggests that cyclophilin D may modify mitochondrial features by inducing the translocation of molecules to the mitochondria through the mechanism associated with cellular energy metabolism.
      Graphical abstract image

      PubDate: 2016-11-16T15:31:43Z
      DOI: 10.1016/
  • Impact of hypoxia inducible factors on estrogen receptor expression in
           breast cancer cells
    • Authors: Matthias Wolff; Friederike Katharina Kosyna Dunst Wolfgang Jelkmann Reinhard Depping
      Abstract: Publication date: Available online 5 November 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Matthias Wolff, Friederike Katharina Kosyna, Jürgen Dunst, Wolfgang Jelkmann, Reinhard Depping
      In women breast cancer is still the most commonly diagnosed cancer. This type of cancer is classified as a hormone-dependent tumor. Estrogen receptor (ER) expression and functional status contribute to breast cancer development and progression. Another important factor associated with cancer is hypoxia which is defined as the state of reduced oxygen availability in tissues. Intratumoral hypoxia results in the activation of the hypoxia inducible factors (HIFs). HIFs are heterodimeric transcription factors involved in the regulation of many cellular processes, such as angiogenesis, anaerobic metabolism, cell proliferation/survival, and promotion of metastasis. In this study we evaluated the interplay between hypoxia, HIF stabilization and the ER-α/β-ratio in several ER-positive breast cancer cell lines. Hypoxia was shown to inhibit ER expression in ER-positive breast cancer cells. Further experiments using the hypoxia mimetic CoCl2 and HIF-1α knockdown cells indicated that the influence of hypoxia on breast cancer cells involves other pathways than the molecular oxygen sensing pathway. Moreover, we demonstrated that MCF-7 cells in long-term culture lost part of their ability to respond to hypoxic incubation. Understanding the relationships between HIF, ER-α and ER-β expression holds the promise of the development of new therapeutic agents and may provide future advances in prognosis.

      PubDate: 2016-11-09T15:20:08Z
  • Cytotoxicity of prion protein-derived cell-penetrating peptides is
           modulated by pH but independent of amyloid formation
    • Authors: Vineeth Mukundan; Christy Maksoudian Maria Vogel Ibrahim Chehade Marios Katsiotis
      Abstract: Publication date: Available online 3 November 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Vineeth Mukundan, Christy Maksoudian, Maria C. Vogel, Ibrahim Chehade, Marios S. Katsiotis, Saeed M. Alhassan, Mazin Magzoub
      Prion diseases are associated with conversion of cellular prion protein (PrPC) into an abnormally folded and infectious scrapie isoform (PrPSc). We previously showed that peptides derived from the unprocessed N-termini of mouse and bovine prion proteins, mPrP1-28 and bPrP1-30, function as cell-penetrating peptides (CPPs), and destabilize model membrane systems, which could explain the infectivity and toxicity of prion diseases. However, subsequent studies revealed that treatment with mPrP1-28 or bPrP1-30 significantly reduce PrPSc levels in prion-infected cells. To explain these seemingly contradictory results, we correlated the aggregation, membrane perturbation and cytotoxicity of the peptides with their cellular uptake and intracellular localization. Although the peptides have a similar primary sequence, mPrP1-28 is amyloidogenic, whereas bPrP1-30 forms smaller oligomeric or non-fibrillar aggregates. Surprisingly, bPrP1-30 induces much higher cytotoxicity than mPrP1-28, indicating that amyloid formation and toxicity are independent. The toxicity is correlated with prolonged residence at the plasma membrane and membrane perturbation. Both ordered aggregation and toxicity of the peptides are inhibited by low pH. Under non-toxic conditions, the peptides are internalized by lipid-raft dependent macropinocytosis and localize to acidic lysosomal compartments. Our results shed light on the antiprion mechanism of the prion protein-derived CPPs and identify a potential site for PrPSc formation.

      PubDate: 2016-11-09T15:20:08Z
  • 13C kinetic isotope effects on the reaction of a flavin amine oxidase
           determined from whole molecule isotope effects
    • Authors: José R. Tormos; Marina B. Suarez; Paul F. Fitzpatrick
      Abstract: Publication date: Available online 1 November 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): José R. Tormos, Marina B. Suarez, Paul F. Fitzpatrick
      A large number of flavoproteins catalyze the oxidation of amines. Because of the importance of these enzymes in metabolism, their mechanisms have previously been studied using deuterium, nitrogen, and solvent isotope effects. While these results have been valuable for computational studies to distinguish among proposed mechanisms, a measure of the change at the reacting carbon has been lacking. We describe here the measurement of a 13C kinetic isotope effect for a representative amine oxidase, polyamine oxidase. The isotope effect was determined by analysis of the isotopic composition of the unlabeled substrate, N, N’-dibenzyl-1,4-diaminopropane, to obtain a pH-independent value of 1.025. The availability of a 13C isotope effect for flavoprotein-catalyzed amine oxidation provides the first measure of the change in bond order at the carbon involved in this carbon-hydrogen bond cleavage and will be of value to understanding the transition state structure for this class of enzymes.
      Graphical abstract image

      PubDate: 2016-11-02T14:49:35Z
      DOI: 10.1016/
  • Probing the orientation of inhibitor and epoxy-eicosatrienoic acid binding
           in the active site of soluble epoxide hydrolase
    • Authors: Kin Sing Stephen Lee; Niel M. Henriksen; Connie J. Ng; Jun Yang; Weitao Jia; Christophe Morisseau; Armann Andaya; Michael K. Gilson; Bruce D. Hammock
      Abstract: Publication date: Available online 29 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kin Sing Stephen Lee, Niel M. Henriksen, Connie J. Ng, Jun Yang, Weitao Jia, Christophe Morisseau, Armann Andaya, Michael K. Gilson, Bruce D. Hammock
      Soluble epoxide hydrolase (sEH) is an important therapeutic target of many diseases, such as chronic obstructive pulmonary disease (COPD) and diabetic neuropathic pain. It acts by hydrolyzing and thus regulating specific bioactive long chain polyunsaturated fatty acid epoxides (lcPUFA), like epoxyeicosatrienoic acids (EETs). To better predict which epoxides could be hydrolyzed by sEH, one needs to dissect the important factors and structural requirements that govern the binding of the substrates to sEH. This knowledge allows further exploration of the physiological role played by sEH. Unfortunately, a crystal structure of sEH with a substrate bound has not yet been reported. In this report, new photoaffinity mimics of a sEH inhibitor and EET were prepared and used in combination with peptide sequencing and computational modeling, to identify the binding orientation of different regioisomers and enantiomers of EETs into the catalytic cavity of sEH. Results indicate that the stereochemistry of the epoxide plays a crucial role in dictating the binding orientation of the substrate.
      Graphical abstract image

      PubDate: 2016-11-02T14:49:35Z
      DOI: 10.1016/
  • An insight into fusion technology aiding efficient recombinant protein
           production for functional proteomics
    • Authors: Dinesh K. Yadav; Neelam Yadav; Sarika Yadav; Shafiul Haque; Narendra Tuteja
      Abstract: Publication date: Available online 19 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Dinesh K. Yadav, Neelam Yadav, Sarika Yadav, Shafiul Haque, Narendra Tuteja
      Advancements in peptide fusion technologies to maximize the protein production has taken a big leap to fulfill the demands of post-genomics era targeting elucidation of structure/function of the proteome and its therapeutic applications, by over-expression in heterologous expression systems. Despite being most preferred protein expression system armed with variety of cardinal fusion tags, expression of the functionally active recombinant protein in E. coli remains plagued. The present review critically analyses the aptness of well-characterized fusion tags utilized for over-expression of recombinant proteins with improved solubility and their compatibility with downstream purification procedures. The combinatorial tandem affinity strategies have shown to provide more versatile options. Solubility decreasing fusion tags have proved to facilitate the overproduction of antimicrobial peptides. Efficient removal of fusion tags prior to final usage is of utmost importance and has been summarized discussing the efficiency of various enzymatic and chemical methods of tag removal. Unfortunately, no single fusion tag works as a magic bullet to completely fulfill the requirements of protein expression and purification in active form. The information provided might help in selection and development of a successful protocol for efficient recombinant protein production for functional proteomics.

      PubDate: 2016-10-27T22:46:44Z
      DOI: 10.1016/
  • Neutrophils recruited to the myocardium after acute experimental
           myocardial infarct generate hypochlorous acid that oxidizes cardiac
    • Authors: Xiao Suo Wang; Hyun Bo Kim; Andrea Szuchman-Sapir; Aisling McMahon; Joanne M. Dennis; Paul K. Witting
      Abstract: Publication date: Available online 24 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Xiao Suo Wang, Hyun Bo Kim, Andrea Szuchman-Sapir, Aisling McMahon, Joanne M. Dennis, Paul K. Witting
      Myocardial inflammation following acute myocardial infarct (AMI) is associated with risk of congestive heart failure. Pro-inflammatory neutrophils were recruited to the damaged myocardium 24 h after permanent coronary ligation in rats to induce AMI as judged by the presence of immune-positive myeloperoxidase (MPO) in the tissues; MPO generates the oxidant hypochlorous acid (HOCl). Neutrophils were absent in hearts from Control (untreated) and surgical Sham. Similarly, rats exposed to 1 h coronary ligation (Ischemia) showed no neutrophil infiltrate. Concomitantly, MPO activity increased in left ventricular (LV) homogenates prepared from the AMI group and this was inhibited by paracetamol and the nitroxide TEMPO. The same LV-homogenates showed increased 3-chlorotyrosine/tyrosine ratios (biomarker for MPO-activity). Combined 2D gel/Western blot indicated cardiac myoglobin (Mb) was modified after AMI. Subsequent MALDI-TOF and LC-MS/MS analysis of isolated protein spots revealed increased Mb oxidation in hearts from the AMI group relative to Control, Sham and Ischemia groups. Peptide mass mapping revealed oxidation of Met9 and Met132 to the corresponding sulfoxides yet Cys67 remained unmodified. Therefore, neutrophil-generated HOCl can oxidize cardiac Mb after AMI and this may impact on its function within the affected myocardium: oxidized Mb maybe a useful marker of myocardial inflammation.
      Graphical abstract image

      PubDate: 2016-10-27T22:46:44Z
      DOI: 10.1016/
  • Repositioning nordihydroguaiaretic acid as a potent inhibitor of systemic
           amyloidosis and associated cellular toxicity
    • Authors: Saima Nusrat; Nida Zaidi; Masihuz Zaman; Sehbanul Islam; Mohammad Rehan Ajmal; Mohammad Khursheed Siddiqi; Manas Kumar Santra; Rizwan Hasan Khan
      Abstract: Publication date: Available online 24 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Saima Nusrat, Nida Zaidi, Masihuz Zaman, Sehbanul Islam, Mohammad Rehan Ajmal, Mohammad Khursheed Siddiqi, Manas Kumar Santra, Rizwan Hasan Khan
      Although the cure of amyloid related neurodegenerative diseases, non-neuropathic amyloidogenic diseases and non-neuropathic systemic amyloidosis are appealing energetic research attempts, beneficial medication is still to be discovered. There is a need to explore intensely stable therapeutic compounds, potent enough to restrict, disrupt or wipe out such toxic aggregates. We had performed a comprehensive biophysical, computational and cell based assay, that shows Nordihydroguaiaretic acid (NA) not only significantly inhibits heat induced hen egg white lysozyme (HEWL) fibrillation but also disaggregates preformed HEWL fibrils and reduces the cytoxicity of amyloid fibrils as well as disaggregated fibrillar species. The inhibitory potency of NA was determined by an IC50 of 26.3 μM. NA was also found to effectively inhibit human lysozyme (HL) fibrillation. NA interferes in the amyloid fibrillogenesis process by interacting hydrophobically with the amino acid residues found in highly prone amyloid fibril forming region of HEWL as explicated by molecular docking results. The results recommend NA as a probable neuroprotective and promising inhibitor for the therapeutic advancement prospective against amyloid related diseases.
      Graphical abstract image

      PubDate: 2016-10-27T22:46:44Z
      DOI: 10.1016/
  • Reciprocal regulation of acetyl-CoA carboxylase 1 and senescence in human
           fibroblasts involves oxidant mediated p38 MAPK activation
    • Authors: Inés Marmisolle; Jennyfer Martínez; Jie Liu; Mauricio Mastrogiovanni; María M. Fergusson; Ilsa I. Rovira; Laura Castro; Andrés Trostchansky; María Moreno; Liu Cao; Toren Finkel; Celia Quijano
      Abstract: Publication date: Available online 27 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Inés Marmisolle, Jennyfer Martínez, Jie Liu, Mauricio Mastrogiovanni, María M. Fergusson, Ilsa I. Rovira, Laura Castro, Andrés Trostchansky, María Moreno, Liu Cao, Toren Finkel, Celia Quijano
      We sought to explore the fate of the fatty acid synthesis pathway in human fibroblasts exposed to DNA damaging agents capable of inducing senescence, a state of irreversible growth arrest. Induction of premature senescence by doxorubicin or hydrogen peroxide led to a decrease in protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1), the enzyme that catalyzes the rate-limiting step in fatty-acid biosynthesis. ACC1 decay accompanied the activation of the DNA damage response (DDR), and resulted in decreased lipid synthesis. A reduction in protein and mRNA levels of ACC1 and in lipid synthesis was also observed in human primary fibroblasts that underwent replicative senescence. We also explored the consequences of inhibiting fatty acid synthesis in proliferating non-transformed cells. Using shRNA technology, we knocked down ACC1 in human fibroblasts. Interestingly, this metabolic perturbation was sufficient to arrest proliferation and trigger the appearance of several markers of the DDR and increase senescence associated β-galactosidase activity. Reactive oxygen species and p38 mitogen activated protein kinase phosphorylation participated in the induction of senescence. Similar results were obtained upon silencing of fatty acid synthase (FAS) expression. Together our results point towards a tight coordination of fatty acid synthesis and cell proliferation in human fibroblasts.
      Graphical abstract image

      PubDate: 2016-10-27T22:46:44Z
      DOI: 10.1016/
  • Development of the first internally-quenched fluorescent substrates of
           human cathepsin C: The application in the enzyme detection in biological
    • Authors: Monika Łęgowska; Yveline Hamon; Anna Wojtysiak; Renata Grzywa; Marcin Sieńczyk; Timo Burster; Brice Korkmaz; Adam Lesner
      Abstract: Publication date: Available online 13 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Monika Łęgowska, Yveline Hamon, Anna Wojtysiak, Renata Grzywa, Marcin Sieńczyk, Timo Burster, Brice Korkmaz, Adam Lesner
      Cathepsin C is a wildly expressed cysteine exopeptidase that is mostly recognized for the activation of the granule-associated proinflammatory serine proteases in neutrophils, cytotoxic T lymphocytes and mast cells. It has been shown that the enzyme can be secreted extracellularly; however, its occurrence in human bodily fluids/physiological samples has not been thoroughly studied. In the course of this study, the first fluorescence resonance energy transfer peptides for the measurement of the activity of human cathepsin C were designed and synthesized. Two series of tetra- and pentapeptide substrates enabled the detailed S′ specificity study of cathepsin C, which has been examined for the first time. The extensive enzymatic studies of the obtained compounds resulted in the selection of the highly specific and selective substrate Thi-Ala(Mca)-Ser-Gly-Tyr(3-NO2)-NH2, which was successfully employed for the detection of cathepsin C activity in complex biological samples such as cell lysates, urine and bronchoalveolar lavage fluids. Molecular docking of the selected substrate was performed in order to better understand the binding mode of the substrates in the active site of cathepsin C.

      PubDate: 2016-10-19T12:26:14Z
      DOI: 10.1016/
  • Ligand binding phenomena that pertain to the metabolic function of
    • Authors: Brett A. Beaupre; Joseph V. Roman; Matthew R. Hoag; Kathleen M. Meneely; Nicholas R. Silvaggi; Audrey L. Lamb; Graham R. Moran
      Abstract: Publication date: Available online 18 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Brett A. Beaupre, Joseph V. Roman, Matthew R. Hoag, Kathleen M. Meneely, Nicholas R. Silvaggi, Audrey L. Lamb, Graham R. Moran
      Renalase catalyzes the oxidation of isomers of β-NAD(P)H that carry the hydride in the 2 or 6 positions of the nicotinamide base to form β-NAD(P)+. This activity is thought to alleviate inhibition of multiple β-NAD(P)-dependent enzymes of primary and secondary metabolism by these isomers. Here we present evidence for a variety of ligand binding phenomena relevant to the function of renalase. We offer evidence of the potential for primary metabolism inhibition with structures of malate dehydrogenase and lactate dehydrogenase bound to the 6-dihydroNAD isomer. The previously observed preference of renalase from Pseudomonas for NAD-derived substrates over those derived from NADP is accounted for by the structure of the enzyme in complex with NADPH. We also show that nicotinamide nucleosides and mononucloetides reduced in the 2- and 6-positions are renalase substrates, but bind weakly. A seven-fold enhancement of acquisition (kred/K d) for 6-dihydronicotinamide riboside was observed for human renalase in the presence of ADP. However, generally the addition of complement ligands, ADP for mononucloetide or AMP for nucleoside substrates, did not enhance the reductive half-reaction. Non-substrate nicotinamide nucleosides or nucleotides bind weakly suggesting that only β-NADH and β-NADPH compete with dinucleotide substrates for access to the active site.
      Graphical abstract image

      PubDate: 2016-10-19T12:26:14Z
      DOI: 10.1016/
  • Photoacoustic calorimetry studies of CO photo-dissociation from
           chloramine-T modified horse heart cytochrome-c
    • Authors: Tarah A. Word; Randy W. Larsen
      Abstract: Publication date: Available online 4 October 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Tarah A. Word, Randy W. Larsen
      Treatment of horse heart Cytochrome-c (Cc) with N-chloro-4-toluosulfonamide (Chloramine-t, CT) results in the oxidation of methionine (Met) residues to the corresponding sulfoxide including the distal heme ligand, Met80. The resulting Fe-sulfoxide coordination is sufficiently labile in the ferrous form to be displaced by gaseous ligands, including CO. Photolysis of the CO-CT-Cc complex provides an opportunity to examine ligand binding dynamics that are associated with a relatively rigid distal heme pocket. In this work, photoacoustic calorimetry (PAC) was utilized to obtain the kinetics as well as enthalpy and molar volume changes subsequent to CO photo-dissociation from CO-CT-Cc. Previous photolysis studies of CO-CT-Cc have led to a proposed model for ligand recombination in which the Met80-sulfoxide and CO recombine with the heme on relatively slow timescales (50 μs and ∼500 μs, respectively). The PAC data presented here reveals two additional kinetic phases with lifetimes of <20 ns and 534 ± 75 ns. The fast phase (<20 ns) is associated with an ΔH of 44 ± 5 kcal mol−1 and ΔV of −0.5 ± 0.5 mL mol−1, whereas the slower phase (534 ns) is associated with a small ΔH of 2 ± 3 kcal mol−1 and ΔV of 1 ± 0.5 mL mol−1.
      Graphical abstract image

      PubDate: 2016-10-06T16:07:59Z
      DOI: 10.1016/
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
Home (Search)
Subjects A-Z
Publishers A-Z
Your IP address:
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2016