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BIOCHEMISTRY (218 journals)                  1 2     

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AAPS PharmSciTech     Hybrid Journal   (Followers: 4)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Central Science     Hybrid Journal   (Followers: 1)
ACS Chemical Biology     Full-text available via subscription   (Followers: 133)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 14)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 10)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 7)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 8)
Advances in Biological Chemistry     Open Access   (Followers: 5)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 12)
African Journal of Biochemistry Research     Open Access   (Followers: 1)
African Journal of Chemical Education     Open Access   (Followers: 2)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
American Journal of Biochemistry     Open Access   (Followers: 5)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 68)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 12)
American Journal of Polymer Science     Open Access   (Followers: 20)
Amino Acids     Hybrid Journal   (Followers: 8)
Analytical Biochemistry     Hybrid Journal   (Followers: 137)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 8)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 47)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 8)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 42)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 14)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 5)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 20)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (Followers: 1)
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Asian Journal of Biomedical and Pharmaceutical Sciences     Open Access   (Followers: 2)
Avicenna Journal of Medical Biochemistry     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 17)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 4)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 12)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 26)
Biochemical Pharmacology     Hybrid Journal   (Followers: 8)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 3)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 197)
Biochemistry & Pharmacology : Open Access     Open Access   (Followers: 1)
Biochemistry & Physiology : Open Access     Open Access  
Biochemistry (Moscow)     Hybrid Journal   (Followers: 3)
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 Cell Biology     Full-text available via subscription   (Followers: 15)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 5)
Biochemistry and Molecular Biology of Fishes     Full-text available via subscription   (Followers: 1)
Biochemistry Research International     Open Access   (Followers: 4)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 6)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 15)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 6)
Biochimie     Hybrid Journal   (Followers: 5)
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 28)
BioDrugs     Full-text available via subscription   (Followers: 8)
Bioelectrochemistry     Hybrid Journal   (Followers: 1)
Biofuels     Hybrid Journal   (Followers: 10)
Biogeochemistry     Hybrid Journal   (Followers: 9)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 26)
Biomaterials Research     Open Access   (Followers: 2)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Hybrid Journal   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 25)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 45)
Bitácora Digital     Open Access  
BMC Biochemistry     Open Access   (Followers: 12)
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca : Food Science and Technology     Open Access  
Carbohydrate Polymers     Hybrid Journal   (Followers: 7)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 5)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 4)
Central European Journal of Chemistry     Hybrid Journal   (Followers: 6)
ChemBioChem     Hybrid Journal   (Followers: 6)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 22)
Chemical Engineering Journal     Hybrid Journal   (Followers: 21)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Open Access   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 3)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 4)
Chemistry & Biology     Full-text available via subscription   (Followers: 29)
Chemistry and Ecology     Hybrid Journal  
ChemTexts     Hybrid Journal  
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 19)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 60)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 4)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 1)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 7)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 2)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 10)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 4)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 21)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 5)
DNA Barcodes     Open Access  
Doklady Biochemistry and Biophysics     Hybrid Journal   (Followers: 1)
Doklady Chemistry     Hybrid Journal  
Egyptian Journal of Biochemistry and Molecular Biology     Full-text available via subscription  
FABICIB     Open Access  
FEBS Letters     Hybrid Journal   (Followers: 58)
FEBS Open Bio     Open Access   (Followers: 3)
Fish Physiology and Biochemistry     Hybrid Journal   (Followers: 3)
Food & Function     Full-text available via subscription   (Followers: 5)
Foundations of Modern Biochemistry     Full-text available via subscription  
Free Radicals and Antioxidants     Full-text available via subscription   (Followers: 3)
Frontiers in Molecular Biosciences     Open Access   (Followers: 2)
Frontiers in Natural Product Chemistry     Hybrid Journal  
Global Biogeochemical Cycles     Full-text available via subscription   (Followers: 7)
Green Chemistry     Full-text available via subscription   (Followers: 9)
Histochemistry and Cell Biology     Hybrid Journal   (Followers: 4)
Indian Journal of Biochemistry and Biophysics (IJBB)     Open Access   (Followers: 3)
Indian Journal of Clinical Biochemistry     Hybrid Journal  
Indonesian Biomedical Journal     Open Access  
Insect Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 3)
International Journal of Biochemistry & Cell Biology     Hybrid Journal   (Followers: 6)
International Journal of Biochemistry and Biophysics     Open Access  
International Journal of Biological Chemistry     Open Access   (Followers: 4)
International Journal of Food Contamination     Open Access  
International Journal of Plant Research     Open Access   (Followers: 3)
International Journal of Secondary Metabolite     Open Access   (Followers: 1)
Invertebrate Immunity     Open Access   (Followers: 1)
JBIC Journal of Biological Inorganic Chemistry     Hybrid Journal   (Followers: 4)
Journal of Microbial & Biochemical Technology     Open Access   (Followers: 1)
Journal of Applied Biology & Biotechnology     Open Access   (Followers: 1)
Journal of Bioactive and Compatible Polymers     Hybrid Journal   (Followers: 2)
Journal of Biochemistry     Hybrid Journal   (Followers: 42)
Journal of Biological and Information Sciences     Open Access  
Journal of Biological Chemistry     Full-text available via subscription   (Followers: 161)
Journal of Biomaterials Science, Polymer Edition     Hybrid Journal   (Followers: 9)
Journal of Carbohydrate Chemistry     Hybrid Journal   (Followers: 7)
Journal of Cellular Biochemistry     Hybrid Journal   (Followers: 5)
Journal of Chemical Biology     Hybrid Journal   (Followers: 1)
Journal of Chemical Neuroanatomy     Hybrid Journal  
Journal of Clinical Lipidology     Hybrid Journal   (Followers: 1)
Journal of Comparative Physiology B : Biochemical, Systemic, and Environmental Physiology     Hybrid Journal   (Followers: 3)
Journal of Drug Discovery and Therapeutics     Open Access   (Followers: 1)
Journal of Enzyme Inhibition and Medicinal Chemistry     Hybrid Journal   (Followers: 4)
Journal of Evolutionary Biochemistry and Physiology     Hybrid Journal  
Journal of Food and Drug Analysis     Full-text available via subscription  
Journal of Forensic Toxicology and Pharmacology     Hybrid Journal   (Followers: 3)
Journal of Inborn Errors of Metabolism and Screening     Open Access  
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Investigational Biochemistry     Open Access   (Followers: 2)
Journal of Medical and Biomedical Sciences     Open Access  
Journal of Medical Biochemistry     Open Access   (Followers: 5)
Journal of Medicine and Biomedical Research     Open Access   (Followers: 1)
Journal of Molecular Biochemistry     Open Access   (Followers: 2)
Journal of Neurochemistry     Hybrid Journal   (Followers: 2)
Journal of Pediatric Biochemistry     Hybrid Journal   (Followers: 1)
Journal of Peptide Science     Hybrid Journal   (Followers: 24)
Journal of Photochemistry and Photobiology B: Biology     Hybrid Journal   (Followers: 3)
Journal of Physiobiochemical Metabolism     Hybrid Journal   (Followers: 1)
Journal of Physiology and Biochemistry     Hybrid Journal   (Followers: 3)
Journal of Plant Biochemistry and Biotechnology     Hybrid Journal   (Followers: 5)
Journal of Steroid Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Journal of Virology & Antiviral Research     Hybrid Journal   (Followers: 2)
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 6)
La Rivista Italiana della Medicina di Laboratorio - Italian Journal of Laboratory Medicine     Hybrid Journal  
Marine Chemistry     Hybrid Journal   (Followers: 6)
Molecular and Biochemical Parasitology     Hybrid Journal   (Followers: 2)
Molecular and Cellular Biochemistry     Hybrid Journal   (Followers: 3)
Molecular Informatics     Hybrid Journal   (Followers: 4)
Molecular inhibitors in targeted therapy     Open Access  
Moscow University Chemistry Bulletin     Hybrid Journal   (Followers: 1)
Mycology : An International Journal on Fungal Biology     Hybrid Journal   (Followers: 4)
Natural Products and Bioprospecting     Open Access   (Followers: 3)
Nature Chemical Biology     Full-text available via subscription   (Followers: 65)
Nature Communications     Open Access   (Followers: 95)
Novelty in Biomedicine     Open Access  
Ocean Acidification     Open Access   (Followers: 1)
Organic & Biomolecular Chemistry     Full-text available via subscription   (Followers: 76)
Parasitology Open     Open Access  
Peptidomics     Open Access  
Pesticide Biochemistry and Physiology     Hybrid Journal   (Followers: 4)
Pharmaceutical Bioprocessing     Full-text available via subscription   (Followers: 1)
Pharmacognosy Magazine     Open Access   (Followers: 2)
Pharmacognosy Research     Open Access   (Followers: 3)
Pharmacognosy Reviews     Open Access   (Followers: 1)
Phytochemistry Reviews     Hybrid Journal  
Plant Physiology and Biochemistry     Hybrid Journal   (Followers: 7)
Plasma Chemistry and Plasma Processing     Hybrid Journal   (Followers: 2)
Polymer Journal     Hybrid Journal   (Followers: 1)
Preparative Biochemistry and Biotechnology     Hybrid Journal   (Followers: 4)
Process Biochemistry     Full-text available via subscription   (Followers: 5)
Processes     Open Access  
Progress in Histochemistry and Cytochemistry     Hybrid Journal  
Protist Genomics     Open Access  
Psiquiatría Biológica     Full-text available via subscription  

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
  [SJR: 1.602]   [H-I: 124]   [20 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [2817 journals]
  • Tropomyosin-binding properties modulate competition between tropomodulin
    • Abstract: Publication date: 15 June 2016
      Source:Archives of Biochemistry and Biophysics, Volume 600
      Author(s): Mert Colpan, Natalia A. Moroz, Kevin T. Gray, Dillon A. Cooper, Christian A. Diaz, Alla S. Kostyukova
      The formation and fine-tuning of cytoskeleton in cells are governed by proteins that influence actin filament dynamics. Tropomodulin (Tmod) regulates the length of actin filaments by capping the pointed ends in a tropomyosin (TM)-dependent manner. Tmod1, Tmod2 and Tmod3 are associated with the cytoskeleton of non-muscle cells and their expression has distinct consequences on cell morphology. To understand the molecular basis of differences in the function and localization of Tmod isoforms in a cell, we compared the actin filament-binding abilities of Tmod1, Tmod2 and Tmod3 in the presence of Tpm3.1, a non-muscle TM isoform. Tmod3 displayed preferential binding to actin filaments when competing with other isoforms. Mutating the second or both TM-binding sites of Tmod3 destroyed its preferential binding. Our findings clarify how Tmod1, Tmod2 and Tmod3 compete for binding actin filaments. Different binding mechanisms and strengths of Tmod isoforms for Tpm3.1 contribute to their divergent functional capabilities.

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

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

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

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

      PubDate: 2016-04-30T08:09:27Z
  • Low-temperature atmospheric-pressure plasma sources for plasma medicine
    • Abstract: Publication date: Available online 22 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yuichi Setsuhara
      In this review paper, fundamental overviews of low-temperature atmospheric-pressure plasma generation are provided and various sources for plasma medicine are described in terms of operating conditions and plasma properties.

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

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

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

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

      PubDate: 2016-04-22T16:39:29Z
  • Comparison of free radicals formation induced by cold atmospheric plasma,
           ultrasound, and ionizing radiation
    • Abstract: Publication date: Available online 13 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Mati Ur Rehman, Paras Jawaid, Hidefumi Uchiyama, Takashi Kondo
      Plasma medicine is increasingly recognized interdisciplinary field combining engineering, physics, biochemistry and life sciences. Plasma is classified into two categories based on the temperature applied, namely “thermal” and “non-thermal” (i.e., cold atmospheric plasma). Non-thermal or cold atmospheric plasma (CAP) is produced by applying high voltage electric field at low pressures and power. The chemical effects of cold atmospheric plasma in aqueous solution are attributed to high voltage discharge and gas flow, which is transported rapidly on the liquid surface. The argon-cold atmospheric plasma (Ar-CAP) induces efficient reactive oxygen species (ROS) in aqueous solutions without thermal decomposition. Their formation has been confirmed by electron paramagnetic resonance (EPR) spin trapping, which is reviewed here. The similarities and differences between the plasma chemistry, sonochemistry, and radiation chemistry are explained. Further, the evidence for free radical formation in the liquid phase and their role in the biological effects induced by cold atmospheric plasma, ultrasound and ionizing radiation are discussed.

      PubDate: 2016-04-17T16:33:48Z
  • Tanshinone ⅡA inhibits human esophageal cancer cell growth through
           miR-122-mediated PKM2 down-regulation
    • Abstract: Publication date: 15 May 2016
      Source:Archives of Biochemistry and Biophysics, Volume 598
      Author(s): Hong-Sheng Zhang, Feng-Juan Zhang, Hu Li, Yang Liu, Guang-Yuan Du, Ying-Hui Huang
      Pyruvate kinase M2 (PKM2) plays a pivotal role in the growth, survival and metabolic reprogramming of cancer cells. Here, we presented for the first time that tanshinone ⅡA inhibited human esophagus cancer cell growth through miR-122-mediated PKM2 down-regulation pathway. Tanshinone ⅡA inhibited cell proliferation and induced cell cycle arrest in S phase in human Ec109 cells. As expected, tanshinone ⅡA down-regulated PKM2 mRNA and protein expression in Ec109 cells. Given these findings, we further investigated microRNAs regulation of PKM2 and confirmed miR-122 for targeting PKM2. Moreover, we found that tanshinone ⅡA-induced up-regulation of miR-122 expression inhibited PKM2 expression in Ec109 cells. Meanwhile, tanshinone ⅡA inhibited proliferation through miR122-medated PKM2 down-regulation. It was demonstrated that the anticancer activity of tanshinone ⅡA was targeted at metabolic regulation of miR-122/PKM2 in human esophagus cancer cells. Taken together, our results revealed tanshinone ⅡA targeting at PKM2-mediated metabolic reprogramming play an important role in inhibition of esophageal cancer cell growth.

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

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

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

      PubDate: 2016-04-10T00:03:59Z
  • Oxidative stress as an iceberg in carcinogenesis and cancer biology
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Shinya Toyokuni
      After the conquest of numerous infectious diseases, the average life span for humans has been enormously prolonged, reaching more than 80 years in many developed countries. However, cancer is one of the top causes of death, and its incidence continues to increase in many countries, including Japan. I was deeply influenced during my career as a cancer researcher by the concept of oxidative stress, which was established by Helmut Sies in 1985. I have no doubt that oxidative stress is a major cause of carcinogenesis in humans but that other factors and chemicals modify it. Notably, established cancer cells are more oxidatively stressed than their non-tumorous counterparts are, and this stress may be associated with selection under oxidative stress and, thus, faster proliferation compared with non-tumorous cells. For cancer prevention, both avoidance of specific risks that are associated with genetic susceptibility and decreasing oxidative stress in general should delay carcinogenesis. For cancer therapy, individualization and precision medicine require further research in the future. In addition to the currently burgeoning array of humanized antibodies and protein kinase inhibitors, novel methods to increase oxidative stress only in cancer cells would be helpful.

      PubDate: 2016-04-10T00:03:59Z
  • Leveraging oxidative stress questions in vivo: Implications and
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Gavin E. Arteel
      The elegance of Helmut Sies' original definition of oxidative stress belies the complexity of the reactions that are potentially involved. This is by no means a criticism of the author, but rather how the words have been used to oversimplify the concept by some. Reactive oxygen and nitrogen species (ROS and RNS, respectively) can be products of a myriad of events within the living body. Indeed, it is now understood that ROS/RNS are critical for normal cellular metabolism and have beneficial effects (e.g., cytotoxicity against invading bacteria). A general problem of studying prooxidants in vivo is that, due to their inherent reactivity, they generally cannot be measured directly. This indirect detection of ‘footprints’ leaves a very large black box that we are to this day only beginning to understand. This manuscript will summarize some considerations that are of utmost importance when translating oxidative stress into in vivo research. Helmut has been a key thought leader, researcher and mentor whose contributions to this field are immeasurable.

      PubDate: 2016-04-10T00:03:59Z
  • Oxidative stress and antioxidants: Distress or eustress'
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Etsuo Niki
      There is a growing consensus that reactive oxygen species (ROS) are not just associated with various pathologies, but that they act as physiological redox signaling messenger with important regulatory functions. It is sometimes stated that “if ROS is a physiological signaling messenger, then removal of ROS by antioxidants such as vitamins E and C may not be good for human health.” However, it should be noted that ROS acting as physiological signaling messenger and ROS removed by antioxidants are not the same. The lipid peroxidation products of polyunsaturated fatty acids and cholesterol induce adaptive response and enhance defense capacity against subsequent oxidative insults, but it is unlikely that these lipid peroxidation products are physiological signaling messenger produced on purpose. The removal of ROS and inhibition of lipid peroxidation by antioxidants should be beneficial for human health, although it has to be noted also that they may not be an effective inhibitor of oxidative damage mediated by non-radical oxidants. The term ROS is vague and, as there are many ROS and antioxidants which are different in chemistry, it is imperative to explicitly specify ROS and antioxidant to understand the effects and role of oxidative stress and antioxidants properly.

      PubDate: 2016-04-10T00:03:59Z
  • New perspectives: Insights into oxidative stress from bacterial studies
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Gisela Storz
      Studies of the response to hydrogen peroxide as well as the characterization of small, noncoding RNAs and small proteins of less than 50 amino acids in Escherichia coli have given new perspectives on redox sensing, the nature of regulators and gene organization that are relevant to all organisms.

      PubDate: 2016-04-10T00:03:59Z
  • The Oxygen Paradox, oxidative stress, and ageing
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Kelvin J.A. Davies
      Professor Helmut Sies is being lauded in this special issue of Archives of Biochemistry & Biophysics, on the occasion of his retirement as Editor-in-Chief. There is no doubt that Helmut has exerted an enormously positive influence on this journal, the fields of Biochemistry & Biophysics in general, and the areas of free radical and redox biology & medicine in particular. Helmut Sies' many discoveries about peroxide metabolism, glutathione, glutathione peroxidases, singlet oxygen, carotenoids in general and lycopene in particular, and flavonoids, fill the pages of his more than 600 publications. In addition, he will forever be remembered for coining the term ‘oxidative stress’ that is so widely used (and sometimes abused) by most of his colleagues.

      PubDate: 2016-04-10T00:03:59Z
  • Oxidative stress, free radicals and protein peroxides
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Janusz M. Gebicki
      Primary free radicals generated under oxidative stress in cells and tissues produce a cascade of reactive secondary radicals, which attack biomolecules with efficiency determined by the reaction rate constants and target concentration. Proteins are prominent targets because they constitute the bulk of the organic content of cells and tissues and react readily with many of the secondary radicals. The reactions commonly lead to the formation of carbon-centered radicals, which generally convert in vivo to peroxyl radicals and finally to semistable hydroperoxides. All of these intermediates can initiate biological damage. This article outlines the advantages of the application of ionizing radiations to studies of radicals, with particular reference to the generation of desired radicals, studies of the kinetics of their reactions and correlating the results with events in biological systems. In one such application, formation of protein hydroperoxides in irradiated cells was inhibited by the intracellular ascorbate and glutathione.
      Graphical abstract image

      PubDate: 2016-04-10T00:03:59Z
  • Publishers note – Tribute issue to Helmut Sies
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Anthony Newman

      PubDate: 2016-04-10T00:03:59Z
  • Tribute issue: Helmut Sies and oxidative stress: Venit, vidit, vicit
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Henry Jay Forman, Shinya Toyokuni

      PubDate: 2016-04-10T00:03:59Z
  • Helmut Sies and the compartmentation of hydroperoxide metabolism
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Leopold Flohé
      The early work of Helmut Sies on mammalian hydroperoxide metabolism is reviewed with particular emphasis on the in situ function of catalase and glutathione peroxidase1. Starting out from a catalase-dominated thinking in the middle of the last century, Sies first demonstrated, by whole organ spectroscopy, that H2O2 is generated in rat liver and metabolized by catalase. In a joined effort with the author's group, he then worked out that glutathione peroxidase can kinetically compete with catalase in hydroperoxide metabolism in situ. In compartmentalized cells, however, the “competition” of the two enzymes turned out to be a mutual complementation because of their different subcellular location. The studies for the first time documented that the metabolism of freely diffusible hydroperoxides is compartmentalized and, thus, paved the way to a better understanding of oxidant challenges and redox regulation. The article, garnished with personal memories, is meant as a nostalgic journey though ancient times of biochemistry with their changing fashions and paradigms, revealing the roots of topical perspectives and controversies in redox biology.

      PubDate: 2016-04-10T00:03:59Z
  • Hydrogen peroxide, from Wieland to Sies
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Willem H. Koppenol
      A history of the formation of hydrogen peroxide in vivo is presented, starting with the discovery of catalase. The first hypothesis was formulated by Heinrich Wieland, who assumed that dioxygen reacted directly with organic molecules. This view was strongly criticised by Otto Warburg, Helmut Sies' academic grandfather. The involvement of hydrogen peroxide in physiological processes was investigated by Theodor Bücher, the “Doktorvater” of Helmut. Helmut's research made it possible to quantitate hydrogen peroxide in tissues.

      PubDate: 2016-04-10T00:03:59Z
  • Hydrogen peroxide and central redox theory for aerobic life
    • Abstract: Publication date: 1 April 2016
      Source:Archives of Biochemistry and Biophysics, Volume 595
      Author(s): Dean P. Jones
      When Rafael Radi and I wrote about Helmut Sies for the Redox Pioneer series, I was disappointed that the Editor restricted us to the use of “Pioneer” in the title. My view is that Helmut was always ahead of the pioneers: He was a scout discovering paths for exploration and a trailblazer developing strategies and methods for discovery. I have known him for nearly 40 years and greatly enjoyed his collegiality as well as brilliance in scientific scholarship. He made monumental contributions to 20th century physiological chemistry beginning with his first measurement of H2O2 in rat liver. While continuous H2O2 production is dogma today, the concept of H2O2 production in mammalian tissues was largely buried for half a century. He continued this leadership in research on oxidative stress, GSH, selenium, and singlet oxygen, during the timeframe when physiological chemistry and biochemistry transitioned to contemporary 21st century systems biology. His impact has been extensive in medical and health sciences, especially in nutrition, aging, toxicology and cancer. I briefly summarize my interactions with Helmut, stressing our work together on the redox code, a set of principles to link mitochondrial respiration, bioenergetics, H2O2 metabolism, redox signaling and redox proteomics into central redox theory.

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

      PubDate: 2016-04-06T08:57:42Z
  • Plasma-on-chip device for stable irradiation of cells cultured in media
           with a low-temperature atmospheric pressure plasma
    • Abstract: Publication date: Available online 5 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Tomohiro Okada, Chun-Yao Chang, Mime Kobayashi, Tetsuji Shimizu, Minoru Sasaki, Shinya Kumagai
      We have developed a micro electromechanical systems (MEMS) device which enables plasma treatment for cells cultured in media. The device, referred to as the plasma-on-chip, comprises microwells and microplasma sources fabricated together in a single chip. The microwells have through-holes between the microwells and microplasma sources. Each microplasma source is located on the backside of each microwells. The reactive components generated by the microplasma sources pass through the through-holes and reach cells cultured in the microwells. In this study, a plasma-on-chip device was modified for a stable plasma treatment. The use of a dielectric barrier discharge (DBD) technique allowed a stable plasma treatment up to 3 min. The plasma-on-chip with the original electrode configuration typically had the maximum stable operation time of around 1 min. Spectral analysis of the plasma identified reactive species such as O and OH radicals that can affect the activity of cells. Plasma treatment was successfully performed on yeast (Saccharomyces cerevisiae) and green algae (Chlorella) cells. While no apparent change was observed with yeast, the treatment degraded the activity of the Chlorella cells and decreased their fluorescence. The device has the potential to help understand interactions between plasma and cells.
      Graphical abstract image

      PubDate: 2016-04-06T08:57:42Z
  • Non-thermal plasma for air and water remediation
    • Abstract: Publication date: Available online 4 April 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Siti Aiasah Hashim, Farah Nadia Dayana binti Samsudin, Wong Chiow San, Khomsaton Abu Bakar, Yap Seong Ling, Mohd. Faiz Mohd. Zin
      A modular typed dielectric barrier discharge (DBD) device is designed and tested for air and water remediation. The module is made of a number of DBD tubes that can be arranged in series or parallel. Each of the DBD tubes comprises inner electrode enclosed with dielectric barrier and arranged as such to provide a gap for the passage of gases. Non-thermal plasma generated in the gap effectively creates gaseous chemical reactions. Its efficacy in the remediation of gas stream containing high NOx, similar to diesel emission and wastewater containing latex, are presented. A six tubes DBD module has successfully removed more than 80% of nitric oxide from the gas stream. In another arrangement, oxygen was fed into a two tubes DBD to generate ozone for treatment of wastewater. Samples of wastewater were collected from a treatment pond of a rubber vulcanization pilot plant. The water pollution load was evaluated by the chemical oxygen demand (COD) and biological oxygen demand (BOD5) values. Preliminary results showed some improvement (about 13%) on the COD after treatment and at the same time had increased the BOD5 by 42%. This results in higher BOD5/COD ratio after ozonation which indicate better biodegradability of the wastewater.

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

      PubDate: 2016-04-06T08:57:42Z
  • Molecular regulation of lactation: The complex and requisite roles for
    • Abstract: Publication date: Available online 6 April 2016
      Source:Archives of Biochemistry and Biophysics
      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: 2016-04-06T08:57:42Z
  • A multiplexed targeted assay for high-throughput quantitative analysis of
           serum methylamines by ultra performance liquid chromatography coupled to
           high resolution mass spectrometry
    • Abstract: Publication date: Available online 30 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hanane Kadar, Justine Dubus, Jérémie Dutot, Lyamine Hedjazi, Suman Srinivasa, Kathleen V. Fitch, Steven K. Grinspoon, Jeremy K. Nicholson, Marc-Emmanuel Dumas, Dominique Gauguier
      Methylamines are biologically-active metabolites present in serum and urine samples, which play complex roles in metabolic diseases. Methylamines can be detected by proton nuclear magnetic resonance (NMR), but specific methods remain to be developed for their routine assay in human serum in clinical settings. Here we developed and validated a novel reliable “methylamine panel” method for simultaneous quantitative analysis of trimethylamine (TMA), its major detoxification metabolite trimethylamine-N-oxide (TMAO), and precursors choline, betaine and L-carnitine in human serum using Ultra Performance Liquid Chromatography (UPLC) coupled to High Resolution Mass Spectrometry (HRMS). Metabolite separation was carried out on a HILIC stationary phase. For all metabolites, the assay was linear in the range of 0.25 to 12.5μmol/L and enabled to reach limit of detection of about 0.10μmol/L. Relative standard deviations were below 16% for the three levels of concentrations. We demonstrated the strong reliability and robustness of the method, which was applied to serum samples from healthy individuals to establish the range of concentrations of the metabolites and their correlation relationships and detect gender differences. Our data provide original information for implementing in a clinical environment a MS-based diagnostic method with potential for targeted metabolic screening of patients at risk of cardiometabolic diseases.

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

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

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

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

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

      PubDate: 2016-03-24T07:12:34Z
  • Acyl-CoA reductase PGN_0723 utilizes succinyl-CoA to generate succinate
           semialdehyde in a butyrate-producing pathway of Porphyromonas gingivalis
    • Abstract: Publication date: Available online 21 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yasuo Yoshida, Mitsunari Sato, Yuichiro Kezuka, Yoshiaki Hasegawa, Keiji Nagano, Jun Takebe, Fuminobu Yoshimura
      The molecular basis of butyrate production in Porphyromonas gingivalis has not been fully elucidated, even though butyrate, a short chain fatty acid (SCFA), can exert both beneficial and harmful effects on a mammalian host. A database search showed that the amino acid sequence of PGN_0723 protein was 50.6% identical with CoA-dependent succinate semialdehyde dehydrogenase (SSADH) in Clostridium kluyveri. By contrast, the protein has limited identity (19.1%) with CoA-independent SSADH in Escherichia coli. Compared with the wild type, growth speed, and final turbidity were lower in the PGN_0723 deletion strain that was constructed by replacing the PGN_0723 gene with an erythromycin resistance cassette. Gas chromatography mass spectrometry revealed the supernatant concentrations of the SCFAs butyrate, isobutyrate, and isovalerate, but not propionate, in the PGN_0723 deletion strain were also lower than those in the wild type. The wild-type phenotype was restored in a complemented strain. We cloned the PGN_0723 gene, purified the recombinant protein, and computationally constructed its three-dimensional model. A colorimetric assay and liquid chromatography-tandem mass spectrometry analysis demonstrated that the recombinant PGN_0723 produces succinate semialdehyde, which is an intermediate in the P. gingivalis butyrate synthesis pathway, not from succinate but from succinyl-CoA in the presence of NAD(P)H via a ping-pong bi-bi mechanism. Asn110Ala and Cys239Ala mutations resulted in a significant loss of the CoA-dependent PGN_0723 enzymatic activity. The study provides new insights into butyrate production, which constitutes a virulence factor in P. gingivalis.

      PubDate: 2016-03-24T07:12:34Z
  • dsRNA-protein interactions studied by molecular dynamics techniques.
           Unravelling dsRNA recognition by DCL1
    • Abstract: Publication date: Available online 14 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Salvador I. Drusin, Irina P. Suarez, Diego F. Gauto, Rodolfo M. Rasia, Diego M. Moreno
      Double stranded RNA (dsRNA) participates in several biological processes, where RNA molecules acquire secondary structure inside the cell through base complementarity. The double stranded RNA binding domain (dsRBD) is one of the main protein folds that is able to recognize and bind to dsRNA regions. The N-terminal dsRBD of DCL1 in Arabidopsis thaliana (DCL1-1), in contrast to other studied dsRBDs, lacks a stable structure, behaving as an intrinsically disordered protein. DCL1-1 does however recognize dsRNA by acquiring a canonical fold in the presence of its substrate. Here we present a detailed modeling and molecular dynamics study of dsRNA recognition by DCL1-1. We found that DCL1-1 forms stable complexes with different RNAs and we characterized the residues involved in binding. Although the domain shows a binding loop substantially shorter than other homologs, it can still interact with the dsRNA and results in bending of the dsRNA A-type helix. Furthermore, we found that R8, a non-conserved residue located in the first dsRNA binding region, recognizes preferentially mismatched base pairs. We discuss our findings in the context of the function of DCL1-1 within the microRNA processing complex.
      Graphical abstract image

      PubDate: 2016-03-20T06:51:44Z
  • Mutagenic and chemical analyses provide new insight into enzyme activation
           and mechanism of the type 2 iron-sulfur l-serine dehydratase from
           Legionella pneumophila
    • Abstract: Publication date: Available online 10 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Xiao Lan Xu, Gregory A. Grant
      The crystal structure of the Type 2 l-serine dehydratase from Legionella pneumophila (lpLSD), revealed a “tail-in-mouth” configuration where the C-terminal residue acts as an intrinsic competitive inhibitor. This pre-catalytic structure undergoes an activation step prior to catalytic turnover. Mutagenic analysis of residues at or near the active site cleft is consistent with stabilization of substrate binding by many of the same residues that interact with the C-terminal cysteine and highlight the critical role of certain tail residues in activity. pH-rate profiles show that a residue with pK of 5.9 must be deprotonated and a residue with a pK of 8.5 must be protonated for activity. This supports an earlier suggestion that His 61 is the likely catalytic base. An additional residue with a pK of 8.5-9 increases cooperativity when it is deprotonated. This investigation also demonstrates that the Fe-S dehydratases convert the enamine/imine intermediates of the catalytic reaction to products on the enzyme prior to release. This is in contrast to pyridoxyl 5’ phosphate based dehydratases that release an enamine/imine intermediate into solution, which then hydrolyzes to produce the ketoamine product.

      PubDate: 2016-03-15T06:24:19Z
  • Kinetic analysis of bypass of O6- methylguanine by the catalytic core of
           yeast DNA polymerase eta
    • Abstract: Publication date: Available online 11 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Binyan Liu, Qizheng Xue, Shiling Gu, Weiping Wang, Jie Chen, Yingqing Li, Chunxue Wang, Huidong Zhang
      Alkylating agents can form O 6-methylguansine (O 6-MeG). To study the intrinsic kinetic behaviors of bypassing O 6-MeG, we used the catalytic core of yeast DNA polymerase η (Pol ηcore, residues 1-513), instead of the full-length Pol η, to study their elementary steps, eliminating the effects of the C-terminal C2H2 motif on dNTP incorporation. The misincorporation frequencies were 10-4 for G and 0.055 – 0.446 for O 6-MeG. O 6-MeG does not affect the extension efficiency. Pol ηcore showed no fast burst phase for any incorporation opposite G or O 6-MeG. Primer extension was greatly blocked by O 6-MeG and about 67% dTTP, 31% dCTP and 2% dATP were incorporated opposite O 6-MeG. This study provides further understanding of the mutation mechanism of alkylated lesion for yeast DNA polymerase η.

      PubDate: 2016-03-15T06:24:19Z
  • Oral Administration of SR-110, a Peroxynitrite Decomposing Catalyst,
           Enhances Glucose Homeostasis, Insulin Signaling, and Islet Architecture in
           B6D2F1 Mice Fed a High Fat Diet
    • Abstract: Publication date: Available online 10 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Michael Johns, Sakineh Esmaeili Mohsen Abadi, Nehal Malik, Joshua Lee, William L. Neumann, Smita Rausaria, Maryam Imani-Nejad, Timothy McPherson, Joseph Schober, Guim Kwon
      Peroxynitrite has been implicated in type 2 diabetes and diabetic complications. As a follow-up study to our previous work on SR-135 (Arch Biochem Biophys 577-578: 49-59, 2015), we provide evidence that this series of compounds are effective when administered orally, and their mechanisms of actions extend to the peripheral tissues. A more soluble analogue of SR-135, SR-110 (from a new class of Mn(III) bis(hydroxyphenyl)-dipyrromethene complexes) was orally administered for 2 weeks to B6D2F1 mice fed a high fat-diet (HFD). Mice fed a HFD for 4 months gained significantly higher body weights compared to lean diet-fed mice (52±1.5 g vs 34±1.3 g). SR-110 (10 mg/kg daily) treatment significantly reduced fasting blood glucose and insulin levels, and enhanced glucose tolerance as compared to HFD control or vehicle (peanut butter) group. SR-110 treatment enhanced insulin signaling in the peripheral organs, liver, heart, and skeletal muscle, and reduced lipid accumulation in the liver. Furthermore, SR-110 increased insulin content, restored islet architecture, decreased islet size, and reduced tyrosine nitration. These results suggest that a peroxynitrite decomposing catalyst is effective in improving glucose homeostasis and restoring islet morphology and β-cell insulin content under nutrient overload.

      PubDate: 2016-03-10T16:11:05Z
  • Structural analysis of Centrolobium tomentosum seed lectin with
           inflammatory activity
    • Abstract: Publication date: Available online 3 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Alysson Chaves Almeida, Vinicius Jose da Silva Osterne, Mayara Queiroz Santiago, Vanir Reis Pinto-Junior, Jose Caetano Silva-Filho, Claudia Figueiredo Lossio, Francisco Lucas Faustino Nascimento, Ricardo Patricio Honorato Almeida, Claudener Souza Teixeira, Rodrigo Bainy Leal, Plinio Delatorre, Bruno Anderson Matias Rocha, Ana Maria Sampaio Assreuy, Kyria Santiago Nascimento, Benildo Sousa Cavada
      A glycosylated lectin (CTL) with specificity for mannose and glucose has been detected and purified from seeds of Centrolobium tomentosum, a legume plant from Dalbergieae tribe. It was isolated by mannose-sepharose affinity chromatography. The primary structure was determined by tandem mass spectrometry and consists of 245 amino acids, similar to other Dalbergieae lectins. CTL structures were solved from two crystal forms, a monoclinic and a tetragonal, diffracted at 2.25 and 1.9 Å, respectively. The carbohydrate recognition domain (CRD), metal-binding site and glycosylation site were characterized, and the structural basis for mannose/glucose-binding was elucidated. The lectin adopts the canonical dimeric organization of legume lectins. CTL showed acute inflammatory effect in paw edema model. The protein was subjected to ligand screening (dimannosides and trimannoside) by molecular docking, and interactions were compared with similar lectins possessing the same ligand specificity. This is the first crystal structure of mannose/glucose native seed lectin with proinflammatory activity isolated from the Centrolobium genus.

      PubDate: 2016-03-05T16:02:09Z
  • Glutamine protects cardiomyocytes from hypoxia/reoxygenation injury under
           high glucose conditions through inhibition of the transforming growth
           factor-β1-Smad3 pathway
    • Abstract: Publication date: Available online 3 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hong Zhang, Yong-chun Cui, Kai Li, Bai-qing Yang, Xiao-peng Liu, Dong Zhang, Hao Li, Ai-li Wu, Yue Tang
      Activation of transforming growth factor-β1 (TGF-β1)-Smad3 pathway aggravates myocardial ischemia/reperfusion injury (IRI). We previously showed that glutamine (Gln) protects cardiomyocytes from hypoxia/ reoxygenation (H/R) injury under high glucose (HG) conditions. The aim of this study was to investigate whether Gln exerts its protective effect in H/R via inhibiting TGF-β1-Smad3 pathway. In vitro, H9c2 rat cardiomyocytes were treated with Gln with HG (33 mM) and/or H/R. We also performed in vivo experiments in which we treated normal and diabetic rats with Gln or solvent control following IRI. We assessed protein levels of TGF-β1, total Smad3, phosphorylated (p)-Smad3 and cleaved caspase-3 in H9c2 cells and rat myocardium by Western blotting. H9c2 cells treated with HG + H/R exhibited high apoptosis rates, as well as a highly activated TGF-β1-Smad3 pathway. TGF-β1 receptor inhibitor (SB431542) or Smad3 inhibitor (SIS3) reduced HG + H/R induced apoptosis. Similarly, Gln supplementation alleviated apoptosis and decreased p-Smad3 levels. However, Gln’s protective effect was significantly weakened by TGF-β1. Diabetic rats treated with Gln had improved hemodynamics, smaller infarct size after IRI, and a significant decrease in TGF-β1-Smad3 pathway activation. We conclude that Gln inhibits HG + H/R induced activation of the TGF-β1-Smad3 pathway and decreases cell apoptosis in cardiomyocytes.

      PubDate: 2016-03-05T16:02:09Z
  • Comparative in vitro analyses of recombinant maize starch synthases SSI,
           SSIIa, and SSIII reveal direct regulatory interactions and
    • Abstract: Publication date: Available online 3 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Binquan Huang, Peter L. Keeling, Tracie A. Hennen-Bierwagen, Alan M. Myers
      Starch synthases SSI, SSII, and SSIII function in assembling the amylopectin component of starch, but their specific roles and means of coordination are not fully understood. Genetic analyses indicate regulatory interactions among SS classes, and physical interactions among them are known. The N terminal extension of cereal SSIII, comprising up to 1200 residues beyond the catalytic domain, is responsible at least in part for these interactions. Recombinant maize SSI, SSIIa, and full-length or truncated SSIII, were tested for functional interactions regarding enzymatic activity. Amino-terminal truncated SSIII exhibited reduced activity compared to full-length enzyme, and addition of the N terminus to the truncated protein stimulated catalytic activity. SSIII and SSI displayed a negative interaction that reduced total activity in a reconstituted system. These data demonstrate that SSIII is both a catalytic and regulatory factor. SSIII activity was reduced by approximately 50% after brief incubation at 45 °C, suggesting a role in reduced starch accumulation during growth in high temperatures. Buffer effects were tested to address a current debate regarding the SS mechanism. Glucan stimulated the SSIIa and SSIII reaction rate regardless of the buffer system, supporting the accepted mechanism in which glucosyl units are added to exogenous primer substrates.
      Graphical abstract image

      PubDate: 2016-03-05T16:02:09Z
  • Structure of the Thermophilic L-Arabinose Isomerase from Geobacillus
           kaustophilus Reveals Metal-mediated Intersubunit Interactions for Activity
           and Thermostability
    • Abstract: Publication date: Available online 4 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jin Myung Choi, Yong-Jik Lee, Thinh-Phat Cao, Sun-Mi Shin, Min-Kyu Park, Han-Seung Lee, Eric di Luccio, Seong-Bo Kim, Sang-Jae Lee, Sang Jun Lee, Sung Haeng Lee, Dong-Woo Lee
      Thermophilic L-arabinose isomerase (AI), which catalyzes the interconversion of L-arabinose and L-ribulose, can be used to produce D-tagatose, a sugar substitute, from D-galactose. Unlike mesophilic AIs, thermophilic AIs are highly dependent on divalent metal ions for their catalytic activity and thermostability at elevated temperatures. However, the molecular basis underlying the substrate preferences and metal requirements of multimeric AIs remains unclear. Here we report the first crystal structure of the apo and holo forms of thermophilic Geobacillus kaustophilus AI (GKAI) in hexamer form. The structures, including those of GKAI in complex with L-arabitol, and biochemical analyses revealed not only how the substrate-binding site of GKAI is formed through displacement of residues at the intersubunit interface when it is bound to Mn2+, but also revealed the water-mediated H-bonding networks that contribute to the structural integrity of GKAI during catalysis. These observations suggest metal-mediated isomerization reactions brought about by intersubunit interactions at elevated temperatures are responsible for the distinct active site features that promote the substrate specificity and thermostability of thermophilic AIs.

      PubDate: 2016-03-05T16:02:09Z
  • CHNQ, a novel 2-Chloro-1,4-naphthoquinone Derivative of Quercetin, induces
           Oxidative Stress and Autophagy both in vitro and in vivo
    • Abstract: Publication date: Available online 4 March 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Shabnam Enayat, M. Şeyma Ceyhan, Betül Taşkoparan, Milan Stefek, Sreeparna Banerjee
      Quercetin (Qc) shows strong antitumor effects but has limited clinical application due to poor water solubility and bioavailability. In a screening of novel semi-synthetic derivatives of Qc, 3,7-dihydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3-hydroxyphenyl]-5-hydroxychromen-4-one (CHNQ) could ameliorate acetic acid induced acute colitis in vivo more efficiently than Qc. Since inflammation contributes to colorectal cancer (CRC), we have hypothesized that CHNQ may have anti-cancer effects. Using CRC cell lines HCT-116 and HT-29, we report that CHNQ was three-fold more cytotoxic than Qc along with a robust induction of apoptosis. As expected from naphthoquinones such as CHNQ, a strong induction of oxidative stress was observed. This was accompanied by reactive oxygen species (ROS) induced autophagy marked by a dramatic increase in the lipidation of LC3, decreased activation of Akt/PKB, acidic vesicle accumulation and puncta formation in HCT-116 cells treated with CHNQ. Interestingly, an incomplete autophagy was observed in HT-29 cells where CHNQ treatment led to LC3 lipidation, but not the formation of acidic vacuoles. CHNQ-induced cytotoxicity, ROS formation and autophagy were also detected in vivo in S. cerevisiae strain RDKY3615 (WinstonS288C background). Overall, we propose that CHNQ can induce cancer cell death through the induction of oxidative stress, and may be examined further as a potential chemotherapeutic drug.
      Graphical abstract image

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

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

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

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