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BIOCHEMISTRY (215 journals)                  1 2 3     

AAPS PharmSciTech     Hybrid Journal   (Followers: 8)
Acetic Acid Bacteria     Open Access   (Followers: 2)
ACS Chemical Biology     Full-text available via subscription   (Followers: 228)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 16)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 11)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 7)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 9)
Advances in Biological Chemistry     Open Access   (Followers: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 11)
African Journal of Biochemistry Research     Open Access   (Followers: 1)
African Journal of Chemical Education     Open Access   (Followers: 1)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 4)
American Journal of Biochemistry     Open Access   (Followers: 7)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 117)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 11)
American Journal of Polymer Science     Open Access   (Followers: 21)
Amino Acids     Hybrid Journal   (Followers: 6)
Analytical Biochemistry     Hybrid Journal   (Followers: 121)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 36)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 10)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 20)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 9)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 4)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 10)
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: 3)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 14)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 5)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 9)
Biochemical Genetics     Hybrid Journal   (Followers: 3)
Biochemical Journal     Full-text available via subscription   (Followers: 18)
Biochemical Pharmacology     Hybrid Journal   (Followers: 6)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 3)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 4)
Biochemistry     Full-text available via subscription   (Followers: 194)
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: 4)
Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry     Hybrid Journal   (Followers: 3)
Biochemistry and Cell Biology     Full-text available via subscription   (Followers: 11)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 3)
Biochemistry and Molecular Biology of Fishes     Full-text available via subscription   (Followers: 1)
Biochemistry Research International     Open Access   (Followers: 5)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 4)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 16)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 6)
Biochimie     Hybrid Journal   (Followers: 5)
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 14)
BioDrugs     Full-text available via subscription   (Followers: 8)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 11)
Biogeochemistry     Hybrid Journal   (Followers: 9)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 11)
Biomaterials Research     Open Access  
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Hybrid Journal   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 7)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 22)
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: 9)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 6)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 3)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
Central European Journal of Chemistry     Hybrid Journal   (Followers: 6)
ChemBioChem     Hybrid Journal   (Followers: 3)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 22)
Chemical Engineering Journal     Hybrid Journal   (Followers: 24)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Open Access   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 2)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 18)
Chemistry and Ecology     Hybrid Journal   (Followers: 1)
ChemTexts     Hybrid Journal  
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 4)
Clinical Chemistry and Laboratory Medicine     Hybrid Journal   (Followers: 10)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 3)
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: 5)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 2)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)

        1 2 3     

Journal Cover   Archives of Biochemistry and Biophysics
  [SJR: 1.602]   [H-I: 124]   [10 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
   Published by Elsevier Homepage  [2801 journals]
  • Retracted: Multiple co-activator complexes support ligand-induced
           transactivation function of VDR
    • Abstract: Publication date: Available online 14 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kazuyoshi Yamaoka, Masayo Shindo, Kei Iwasaki, Ikuko Yamaoka, Yoko Yamamoto, Hirochika Kitagawa, Shigeaki Kato

      PubDate: 2015-11-21T03:25:06Z
  • MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte
           chemoattractant protein-1 production by targeting inhibiting LACTB in
           THP-1 macrophages
    • Abstract: Publication date: Available online 18 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jing-Bo Lu, Xing-Xing Yao, Jian-Cheng Xiu, Yan-Wei Hu
      Background Increasing evidence has shown that gene beta-lactamases (LACTB) has effect on obesity. Recent study demonstrates that miR-125b-5p is a potential small molecular target to prevent atherosclerosis obliterans which may be inflammation-associated. However, the mechanism underlying miR-125b-5p on arteriosclerosis development, the association between miR-125b-5p and LACTB is still unknown. Methods and results In this study, we found that miR-125b-5p was down-regulated while LACTB was up-regulated in atherosclerotic plaques. Our results showed that LACTB was a potential target of miR-125b-5p based on bioinformatics analyses and dual-luciferase reporter assays. Moreover, miR-125b-5p directly inhibited LACTB protein and mRNA expression by targeting LACTB 3’UTR. Meanwhile, the expression of monocyte chemotactic protein-1 (MCP-1) was decreased by miR-125b-5p mimics treatment in THP-1 macrophages. We also demonstrated that the level of MCP-1 was markedly increased when transfected with LACTB. In addition, the upregulation of MCP-1 expression through miR-125b-5p inhibitors was attenuate by siRNA-LACTB treatment in LPS-stimulated THP-1 macrophages. Conclusions MiR-125b-5p attenuates the secretion of MCP-1 by directly targeting inhibiting LACTB in LPS-stimulated THP-1 macrophages.

      PubDate: 2015-11-21T03:25:06Z
  • Expression, regulation and functional assessment of the 80 amino acid
           Small Adipocyte Factor 1 (Smaf1) protein in adipocytes
    • Abstract: Publication date: 15 January 2016
      Source:Archives of Biochemistry and Biophysics, Volume 590
      Author(s): Gang Ren, Parisa Eskandari, Siqian Wang, Cynthia M. Smas
      The gene for Small Adipocyte Factor 1, Smaf1 (also known as adipogenin, ADIG), encodes a ∼600 base transcript that is highly upregulated during 3T3-L1 in vitro adipogenesis and markedly enriched in adipose tissues. Based on the lack of an obvious open reading frame in the Smaf1 transcript, it is not known if the Smaf1 gene is protein coding or non-coding RNA. Using a peptide from a putative open reading frame of Smaf1 as antigen, we generated antibodies for western analysis. Our studies prove that Smaf1 encodes an adipose-enriched protein which in western blot analysis migrates at ∼10 kDa. Rapid induction of Smaf1 protein occurs during in vitro adipogenesis and its expression in 3T3-L1 adipocytes is positively regulated by insulin and glucose. Moreover, siRNA studies reveal that expression of Smaf1 in adipocytes is wholly dependent on PPARγ. On the other hand, use of siRNA for Smaf1 to nearly abolish its protein expression in adipocytes revealed that Smaf1 does not have a major role in adipocyte triglyceride accumulation, lipolysis or insulin-stimulated pAkt induction. However, immunolocalization studies using HA-tagged Smaf1 reveal enrichment at adipocyte lipid droplets. Together our findings show that Smaf1 is a novel small protein endogenous to adipocytes and that Smaf1 expression is closely tied to PPARγ−mediated signals and the adipocyte phenotype.

      PubDate: 2015-11-21T03:25:06Z
  • Autophagy activation attenuates angiotensin II-induced cardiac fibrosis
    • Abstract: Publication date: Available online 10 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Shenglan Liu, Shaorui Chen, Min Li, Boyu Zhang, Peiye Shen, Peiqing Liu, Dandan Zheng, Yijie Chen, Jianmin Jiang
      Autophagy has been involved in numerous diseases processes. However, little is known about the role of autophagy in cardiac fibrosis. Thus, whether or not angiotensin II (Ang II)-induced autophagy has a regulatory function on cardiac fibrosis was detected in vitro and in vivo. In rat cardiac fibroblasts (CFs) stimulated with Ang II, activated autophagy was observed using transmission electron microscopic analysis (TEM), immunofluorescence and Western blot. In Ang II-infused mice, increased co-localization of LC3 puncta with vimentin was observed. In rat CFs, co-treated with rapamycin (Rapa), an autophagy inducer, Ang II-induced the upregulation of type I collagen (Col-I), fibronectin (FN) was decreased. Conversely, inhibition of autophagy by chloroquine (CQ), an autophagy inhibitor, or knockdown of ATG5, a key component of the autophagy pathway by specific siRNA, aggravated Ang II-mediated the accumulation of Col-I and FN. Furthermore, in C57 BL/6 mice with Ang II infusion, intraperitoneal administration of Rapa ameliorated Ang II-induced cardiac fibrosis and cardiac dysfunction, while CQ treatment not only exacerbated Ang II-mediated cardiac fibrosis and cardiac dysfunction, but also impaired cardiac function. These findings suggest that autophagy may exert a protective role to attenuate excess extracellular matrix (ECM) accumulation in the heart.

      PubDate: 2015-11-13T11:24:47Z
  • Untargeted Metabolite Profiling Reveals that Nitric Oxide Bioynthesis is
           an Endogenous Modulator of Carotenoid Biosynthesis in Deinococcus
           radiodurans and is Required for Extreme Ionizing Radiation Resistance
    • Abstract: Publication date: Available online 10 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Alex Hansler, Qiuying Chen, Yuliang Ma, Steven S. Gross
      Deinococcus radiodurans (Drad) is the most radioresistant organism known. Although mechanisms that underlie the extreme radioresistance of Drad are incompletely defined, resistance to UV irradiation-induced killing was found to be greatly attenuated in an NO synthase (NOS) knockout strain of Drad (Δnos). We now show that endogenous NO production is also critical for protection of Drad against γ-irradiation (3000 Gy), a result of accelerated growth recovery, not protection against killing. NO-donor treatment rescued radiosensitization in Δnos Drad but did not influence radiosensitivity in wild type Drad. To discover molecular mechanisms by which endogenous NO confers radioresistance, metabolite profiling studies were performed. Untargeted LC-MS-based metabolite profiling in Drad quantified relative abundances of 1,425 molecules and levels of 294 of these were altered by >5-fold (p< 0.01). Unexpectedly, these studies identified a dramatic perturbation in carotenoid biosynthetic intermediates in Δnos Drad, including a reciprocal switch in the pathway end-products from deoxydeinoxanthin to deinoxanthin. NO supplementation rescued these nos deletion-associated changes in carotenoid biosynthesis, and fully-restored radioresistance to wildtype levels. Because carotenoids were shown to be important contributors to radioprotection in Drad, our findings suggest that endogenously-produced NO serves to maintain a spectrum of carotenoids critical for Drad’s ability to withstand radiation insult.

      PubDate: 2015-11-13T11:24:47Z
  • Carboxymethyl lysine induces EMT in podocytes through transcription factor
           ZEB2: Implications for podocyte depletion and proteinuria in diabetes
    • Abstract: Publication date: Available online 10 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): P. Anil Kumar, Gavin I. Welsh, G. Raghu, Ram K. Menon, Moin A. Saleem, G. Bhanuprakash Reddy
      Advanced glycation end-products (AGEs) are implicated in the pathogenesis of diabetic nephropathy (DN). N-carboxymethyl-lysine (CML) is one of the predominant AGEs that accumulate in all renal compartments of diabetic patients. Nevertheless, the direct effect of CML on podocyte biology has not been explored. In this study, we demonstrate the induction of the transcription factor Zeb2 in podocytes upon exposure to CML through activation of NF-kB signaling cascade. Zeb2 orchestrates epithelial-mesenchymal transformation (EMT), during which cell-cell and cell-extracellular matrix interactions are feeble and enable epithelial cells to become invasive. CML treatment induced both NF-kB and Zeb2 promoter activity and suppressed E-cadherin promoter activity. Inhibition of NF-kB activity prevented CML dependent induction of Zeb2 and loss of E-cadherin. While the exposure of podocytes to CML results in increased podocyte permeability, shRNA-mediated knockdown of Zeb2 expression abrogated CML-mediated podocyte permeability. Further, in vivo findings of elevated CML levels concurrent with increased expression of ZEB2 in glomeruli and proteinuria in diabetic rats confirm that CML-mediated manifestations in the kidney under chronic diabetes conditions. These in vitro and in vivo results envisage the novel axis of NFkB-ZEB2 in podocytes playing a significant role in eliciting EMT and pathogenesis of DN.

      PubDate: 2015-11-13T11:24:47Z
  • Histone deacetylase inhibitors reduce WB-F344 oval cell viability and
           migration capability by suppressing AKT/mTOR signaling in vitro
    • Abstract: Publication date: Available online 10 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Peng Zhang, Xiaofeng Zhu, Ying Wu, Ronglin Hu, Dongming Li, Jun Du, Xingyuan Jiao, Xiaoshun He
      Histone deacetylase (HDAC) can blockDNA replication and transcription and altered HDAC expressionwas associated with tumorigenesis. This study investigated the effects of HDAC inhibitors on hepatic oval cells and aimed to delineate the underlying molecularevents. Hepatic oval cells were treated with two different HDAC inhibitors, suberoylanilidehydroxamic acid (SAHA) and trichostatin-A (TSA). Cells were subjected tocell morphology, cell viability, cell cycle, and wound healing assays.The expression of proteins related to both apoptosis and the cell cycle, and proteins of the AKT/mammalian target of rapamycin (mTOR) signaling pathway were analyzed by Western blot. The data showed that HDAC inhibitors reduced oval cell viability and migration capability, and arrested oval cells at the G0/G1 and S phases of the cell cycle, in a dose- and time-dependent manner. HDAC inhibitors altered cell morphology and reduced oval cell viability, and downregulated the expression of PCNA, cyclinD1, c-Myc and Bmi1 proteins, while also suppressing AKT/mTOR and its downstream target activity. In conclusion, this study demonstrates that HDAC inhibitors affect oval cells by suppressing AKT/mTOR signaling.

      PubDate: 2015-11-13T11:24:47Z
  • Eicosapentaenoic acid inhibits intestinal β-Carotene absorption by
           downregulation of lipid transporter expression via PPAR-α dependent
    • Abstract: Publication date: Available online 11 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Purna Chandra Mashurabad, Palsa Kondaiah, Ravindranadh Palika, Sudip Ghosh, Madhavan K. Nair, Pullakhandam Raghu
      The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p<0.01) and PPARα agonist (P<0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered β-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of β-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of β-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption.

      PubDate: 2015-11-13T11:24:47Z
  • Novel thrombolytic protein from Cobra venom with Anti-Adhesive Properties
    • Abstract: Publication date: Available online 10 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Chandrasekhar Chanda, Angshuman Sarkar, Dibakar Chakrabarty
      A metalloproteinase anticoagulant toxin of molecular weight 66kDa has been purified from the venom of Indian monocled cobra (Naja kaouthia). This toxin named as NKV 66 cleaved fibrinogen in a dose and time dependent manner. The digestion process was specific to Aα chain and cleaved fibrinogen to peptide fragments. NKV 66 completely liquefied the fibrin clots developed in vitro in 18 hours. Plasma recalcification time and thrombin time were significantly prolonged following treatment of plasma with NKV 66. NKV 66 significantly inhibited ADP and collagen induced platelet aggregation in a dose dependent manner. It showed disintegrin like activity on A549 cells cultured in vitro. About 40% inhibition of adherence of A549 cells to matrix was observed following NKV 66 treatment also NKV 66 treated A549 cells were drastically inhibited from passing through the matrix in cell invasion assays in vitro, suggesting anti-adhesive properties of NKV 66.

      PubDate: 2015-11-13T11:24:47Z
  • The tuberous sclerosis complex model Eker (TSC2+/-) rat exhibits
    • Abstract: Publication date: Available online 6 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yumi Aizawa, Tomomi Shirai, Toshiyuki Kobayashi, Okio Hino, Yoshimasa Tsujii, Hirofumi Inoue, Machiko Kazami, Tadahiro Tadokoro, Tsukasa Suzuki, Ken-Ichi Kobayashi, Yuji Yamamoto
      Tuberous sclerosis complex (TSC) presents as benign tumors that affect the brain, kidneys, lungs and skin. The inactivation of TSC2 gene, through loss of heterozygosity is responsible for tumor development in TSC. Since TSC patients are carriers of heterozygous a TSC2; mutation, to reveal the risk factors which these patients carry prior to tumor development is; important. In this experiment, Eker rat which carry a mutation in this TSC2 gene were; analyzed for their metabolic changes. Wild-type (TSC2+/+) and heterozygous mutant TSC2 (TSC2+/-) Eker rats were raised for 100 days. As a result, the Eker rats were found to exhibit hyperglycemia and hyperketonemia. However the high ketone body production in the liver was observed without accompanying increased levels of plasma free fatty acids or insulin. Further, production of the ketone body β-hydroxybutyrate was inhibited due to the low NADH/NAD+ ratio resulting from the restraint on glycolysis, which was followed by inhibition of the malate-aspartate shuttle and TCA cycle. Therefore, we conclude that glycolysis is restrained in the livers of TSC2 heterozygous mutant rats, and these defects lead to abnormal production of acetoacetate.

      PubDate: 2015-11-09T11:13:48Z
  • Relative Contributions Of L-Fabp, Scp-2/Scp-X, Or Both To Hepatic Biliary
           Phenotype Of Female Mice
    • Abstract: Publication date: Available online 2 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Gregory G. Martin, Danilo Landrock, Kerstin K. Landrock, Philip N. Howles, Barbara P. Atshaves, Ann B. Kier, Friedhelm Schroeder
      Both sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) and liver fatty acid binding protein (L-FABP) have been proposed to function in hepatobiliary bile acid metabolism/accumulation. To begin to address this issue, the impact of ablating L-FABP (LKO) or SCP-2/SCP-x (DKO) individually or both together (TKO) was examined in female mice. Biliary bile acid levels were decreased in LKO, DKO, and TKO mice; however, hepatic bile acid concentration was decreased in LKO mice only. In contrast, biliary phospholipid level was decreased only in TKO mice, while biliary cholesterol levels were unaltered regardless of phenotype. The loss of either or both genes increased hepatic expression of the major bile acid synthetic enzymes (CYP7A1 and/or CYP27A1). Loss of L-FABP and/or SCP-2/SCP-x genes significantly altered the molecular composition of biliary bile acids, but not the proportion of conjugated/unconjugated bile acids or overall bile acid hydrophobicity index. These data suggested that L-FABP was more important in hepatic retention of bile acids, while SCP-2/SCP-x more broadly affected biliary bile acid and phospholipid levels.

      PubDate: 2015-11-05T16:09:05Z
  • The chemical biology of hydropersulfides (RSSH): Chemical stability,
           reactivity and redox roles
    • Abstract: Publication date: 15 December 2015
      Source:Archives of Biochemistry and Biophysics, Volume 588
      Author(s): Simran S. Saund, Victor Sosa, Stephanie Henriquez, Q.Nhu N. Nguyen, Christopher L. Bianco, Shuhei Soeda, Robert Millikin, Corey White, Henry Le, Katsuhiko Ono, Dean J. Tantillo, Yoshito Kumagai, Takaaki Akaike, Joseph Lin, Jon M. Fukuto
      Recent reports indicate the ubiquitous prevalence of hydropersulfides (RSSH) in mammalian systems. The biological utility of these and related species is currently a matter of significant speculation. The function, lifetime and fate of hydropersulfides will be assuredly based on their chemical properties and reactivity. Thus, to serve as the basis for further mechanistic studies regarding hydropersulfide biology, some of the basic chemical properties/reactivity of hydropersulfides was studied. The nucleophilicity, electrophilicity and redox properties of hydropersulfides were examined under biological conditions. These studies indicate that hydropersulfides can be nucleophilic or electrophilic, depending on the pH (i.e. the protonation state) and can act as good one- and two-electron reductants. These diverse chemical properties in a single species make hydropersulfides chemically distinct from other, well-known sulfur containing biological species, giving them unique and potentially important biological function.
      Graphical abstract image

      PubDate: 2015-11-05T16:09:05Z
  • A novel vasorelaxant lectin purified from seeds of Clathrotropis nitida:
           partial characterization and immobilization in chitosan beads
    • Abstract: Publication date: Available online 3 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ana Cecilia Alves, Mayron Alves de Vasconcelos, Mayara Queiroz de Santiago, Vanir Reis Pinto-Junior, Vinicius Jose da Silva Osterne, Claudia Figueiredo Lossio, Pedro Henrique de Souza Ferreira Bringel, Rondinelle Ribeiro de Castro, Celso Shiniti Nagano, Plinio Delatorre, Luiz Augusto Gomes de Souza, Kyria Santiago do Nascimento, Ana Maria Sampaio Assreuy, Benildo Sousa Cavada
      A novel lectin from seeds of Clathrotropis nitida (CNA) was purified and characterized. CNA is a glycoprotein containing approximately 3.3% of carbohydrates in its structure. CNA promoted intense agglutination of rabbit erythrocytes, which was inhibited by galactosides and porcine stomach mucin (PSM). The lectin maintained its hemagglutinating activity after incubation in a wide range of temperatures (30-60 °C) and pH (6.0-7.0), and its binding activity was dependent on divalent cations (Ca+2 and Mg+2). SDS-PAGE showed an electrophoretic profile consisting of a single band of 28 kDa, as confirmed by electrospray ionization mass spectrometry, which indicated an average molecular mass of 27,406±2 Da and the possible presence of isoforms and glycoforms. In addition, CNA exhibited no toxicity to Artemia sp. nauplii and elicited reversible and dose-dependent vasorelaxation in precontracted aortic rings. CNA was successfully immobilized on chitosan beads and was able to capture PSM in solution. This study demonstrated that CNA is a lectin that has potential as a biotechnological tool in glycomics and glycoproteomics applications.

      PubDate: 2015-11-05T16:09:05Z
  • All-trans-retinoic acid and retinol binding to the FA1 site of human serum
           albumin competitively inhibits heme-Fe(III) association
    • Abstract: Publication date: Available online 27 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Elena Di Muzio, Fabio Polticelli, Alessandra di Masi, Gabriella Fanali, Mauro Fasano, Paolo Ascenzi
      Retinoids are a class of chemicals derived from vitamin A metabolism, playing important and diverse functions. Vitamin A, also named all-trans-retinol (all-trans-ROL), is coverted into two classes of biologically active retinoids, i.e. 11-cis-retinoids and acidic retinoids. Among acidic retinoids, all-trans-retinoic acid (all-trans-RA) and 9-cis-retinoic acid (9-cis-RA) represent the main metabolic products. Specific and aspecific proteins solubilize, protect, and detoxify retinoids in the extracellular environment. The retinoid binding protein 4 (RBP4), the epididymal retinoid-binding protein (ERBP), and the interphotoreceptor matrix retinoid-binding protein (IRBP) play a central role in ROL transport, whereas lipocalin-type prostaglandin D synthase (also named β-trace) and human serum albumin (HSA) transport preferentially all-trans-RA. Here, the modulatory effect of all-trans-RA and all-trans-ROL on ferric heme (heme-Fe(III)) binding to HSA is reported. All-trans-RA and all-trans-ROL binding to the FA1 site of HSA competitively inhibit heme-Fe(III) association. Docking simulations and local structural comparison of HSA with all-trans-RA- and all-trans-ROL-binding proteins support functional data indicating the preferential binding of all-trans-RA and all-trans-ROL to the FA1 site of HSA. Present results may be relevant in vivo, in fact HSA could act as a secondary carrier of retinoids in human diseases associated with reduced levels of RBP4 and IRBP.
      Graphical abstract image

      PubDate: 2015-10-28T11:40:48Z
  • Biochemical and Biophysical Characterization of Maize-derived HBsAg for
           the Development of an Oral Vaccine
    • Abstract: Publication date: Available online 28 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Shweta Shah, Celine A. Hayden, Maria E. Fischer, A.Gururaj Rao, John A. Howard
      Although a vaccine against hepatitis B virus (HBV) has been available since 1982, it is estimated that 600,000 people die every year due to HBV. An affordable oral vaccine could help alleviate the disease burden and to this end the hepatitis B surface antigen (HBsAg) was expressed in maize. Orally delivered maize material induced the strongest immune response in mice when lipid was extracted by CO2 supercritical fluid extraction (SFE), compared to full fat and hexane-extracted material. The present study provides a biochemical and biophysical basis for these immunological differences by comparing the active ingredient in the differently treated maize material. Purified maize-derived HBsAg underwent biophysical characterization by gel filtration, transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-CD, and fluorescence. Gel filtration showed that HBsAg forms higher-order oligomers and TEM demonstrated virus-like particle (VLP) formation. The VLPs obtained from SFE were more regular in shape and size compared to hexane or full fat material. In addition, SFE-derived HBsAg showed the greatest extent of α-helical structure by far UV-CD spectrum. Fluorescence experiments also revealed differences in protein conformation. This work establishes SFE-treated maize material as a viable oral vaccine candidate and advances the development of the first oral subunit vaccine.

      PubDate: 2015-10-28T11:40:48Z
  • Characterization of the structural and protein recognition properties of
           hybrid PNA–DNA four-way junctions
    • Abstract: Publication date: 1 December 2015
      Source:Archives of Biochemistry and Biophysics, Volume 587
      Author(s): Douglas Iverson, Crystal Serrano, Ann Marie Brahan, Arik Shams, Filbert Totsingan, Anthony J. Bell
      The objective of this study is to evaluate the structure and protein recognition properties of hybrid four-way junctions (4WJs) composed of DNA and peptide nucleic acid (PNA) strands. We compare a classic immobile DNA junction, J1, vs. six PNA–DNA junctions, including a number with blunt DNA ends and multiple PNA strands. Circular dichroism (CD) analysis reveals that hybrid 4WJs are composed of helices that possess structures intermediate between A- and B-form DNA, the apparent level of A-form structure correlates with the PNA content. The structure of hybrids that contain one PNA strand is sensitive to Mg+2. For these constructs, the apparent B-form structure and conformational stability (Tm) increase in high Mg+2. The blunt-ended junction, b4WJ-PNA3, possesses the highest B-form CD signals and Tm (40.1 °C) values vs. all hybrids and J1. Protein recognition studies are carried out using the recombinant DNA-binding protein, HMGB1b. HMGB1b binds the blunt ended single-PNA hybrids, b4WJ-PNA1 and b4WJ-PNA3, with high affinity. HMGB1b binds the multi-PNA hybrids, 4WJ-PNA1,3 and b4WJ-PNA1,3, but does not form stable protein-nucleic acid complexes. Protein interactions with hybrid 4WJs are influenced by the ratio of A- to B-form helices: hybrids with helices composed of higher levels of B-form structure preferentially associate with HMGB1b.
      Graphical abstract image

      PubDate: 2015-10-24T11:12:33Z
  • Guest Editorial: Special Issue on Metabolomics
    • Abstract: Publication date: Available online 20 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Marc Emmanuel Dumas, Jerzy Adamski, Karsten Suhre

      PubDate: 2015-10-24T11:12:33Z
  • Combined effect of G3139 and TSPO ligands on Ca2+-induced permeability
           transition in rat brain mitochondria
    • Abstract: Publication date: Available online 20 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): T. Azarashvili, O. Krestinina, Yu Baburina, I. Odinokova, D. Grachev, V. Papadopoulos, V. Akatov, J.J. Lemasters, G. Reiser
      Permeability of the mitochondrial outer membrane is determined by the activity of voltage-dependent anion channels (VDAC) which are regulated by many factors and proteins. One of the main partner-regulator of VDAC is the 18 kDa translocator protein (TSPO), whose role in the regulation of membrane permeability is not completely understood. We show that TSPO ligands, 1 μM PPIX and PK11195 at concentrations of 50 μM, accelerate opening of permeability transition pores (mPTP) in Ca2+-overloaded rat brain mitochondria (RBM). By contrast, PK11195 at 100 nM and anti-TSPO antibodies suppressed pore opening. Participation of VDAC in these processes was demonstrated by blocking VDAC with G3139, an 18-mer phosphorothioate oligonucleotides, which sensitized mitochondria to Ca2+-induced mPTP opening. Despite the inhibitory effect of 100 nM PK11195 and anti-TSPO antibodies alone, their combination with G3139 considerably stimulated the mPTP opening. Thus, 100 nM PK11195 and anti-TSPO antibody can modify permeability of the VDAC channel and mPTP. When VDAC channels are closed and TSPO is blocked, permeability of the VDAC for calcium seems to be the highest, which leads to accelerated pore opening.

      PubDate: 2015-10-24T11:12:33Z
  • Metabolome Analyses in Exposome Studies: Profiling Methods for a Vast
           Chemical Space
    • Abstract: Publication date: Available online 19 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Toby Athersuch
      Metabolic profiling (metabonomics/metabolomics) is now used routinely as a tool to provide information-rich datasets for biomarker discovery, prompting and augmenting detailed mechanistic studies. The experimental design and focus of any individual study will be reflected in the types of biomarkers that can be detected; toxicological studies will likely focus on markers of response to insult, whereas clinical case-control studies may yield diagnostic markers of disease. Population studies can make use of omics analyses, including metabonomics, to provide mechanistically-relevant markers that link environmental exposures to chronic disease endpoints. In this article, examples of how metabolic profiling has played a key role in molecular epidemiological analyses of chronic disease are presented, and how these reflect different aspects of the causal pathway. A commentary on the nature of metabolome analysis as a complex mixture analysis problem as opposed to a coded, sequence or template problem is provided, alongside an overview of current and future analytical platforms that are being applied to meet this analytical challenge. Epidemiological studies are an important nexus for integrating various measures of the human exposome, and the ubiquity, diversity and functions of small molecule metabolites, represent an important way to link individual exposures, genetics and phenotype.

      PubDate: 2015-10-24T11:12:33Z
  • Blood, urine and faecal metabolite profiles in the study of adult renal
    • Abstract: Publication date: Available online 21 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Clara Barrios, Tim D. Spector, Cristina Menni
      Chronic kidney disease (CKD) is a major public health burden and to date traditional biomarkers of renal function (such as serum creatinine and cystatin C) are unable to identify at-risk individuals before the disease process is well under way. To help preventive strategies and maximize the potential for effective interventions, it is important to characterise the molecular changes that take place in the development of renal damage. Metabolomics is a promising tool to identify markers of renal disease since the kidneys are involved in the handling of major biochemical classes of metabolites. These metabolite levels capture a snap-shot of the metabolic profile of the individual, allowing for the potential identification of early biomarkers, and the monitoring of real-time kidney function. In this review, we describe the current status of the identification of blood/urine/faecal metabolic biomarkers in different entities of kidney diseases including: acute kidney injury, chronic kidney disease, renal transplant, diabetic nephropathy and other disorders.

      PubDate: 2015-10-24T11:12:33Z
  • Protein structures in Alzheimer's disease: The basis for rationale
           therapeutic design
    • Abstract: Publication date: Available online 22 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Laia Montoliu-Gaya, Sandra Villegas
      Alzheimer's disease (AD) is a neurodegenerative disorder that affects memory, behavior, thinking and emotion. Current therapies to treat AD patients are only capable for temporarily slowing-down the cognitive decline, as they are focused on ameliorating symptoms instead of targeting its underlying causes. The aim of this review is to describe what is known about the protein structures implicated in AD pathogenesis, amyloid cascade members, as well as those structures involved in Aβ clearance. Thus, structural information available for APP, α- β- and γ-secretases, CTFβ and derived Aβ peptides, AICDs, apoE and apoJ, LRP-1 and RAGE, and neprilysin and insulin-degrading enzyme is provided. The recently solved structure for the γ-secretase complex opens the rational design of a new generation of inhibitors, whereas that for Aβ oligomers offers a putative mechanism explaining why monoclonal antibodies targeted to the N-terminus are effective. Then, an overview on therapies targeting some of these molecules presents their benefits and drawbacks. As a general conclusion our knowledge on the protein structures involved in AD has recently substantially advanced, allowing for the rational design of different therapeutic approaches. Hopefully, we are getting closer to finding a strong disease-modifying drug to cure this devastating disease.
      Graphical abstract image

      PubDate: 2015-10-24T11:12:33Z
  • Electrostatics effects on Ca2+ binding and conformational changes in
           EF-hand domains: Functional implications for EF-hand proteins
    • Abstract: Publication date: 1 December 2015
      Source:Archives of Biochemistry and Biophysics, Volume 587
      Author(s): Abdessamad Ababou, Mariola Zaleska
      Mutations of Gln41 and Lys75 with nonpolar residues in the N-terminal domain of calmodulin (N-Cam) revealed the importance of solvation energetics in conformational change of Ca2+ sensor EF-hand domains. While in general these domains have polar residues at these corresponding positions yet the extent of their conformational response to Ca2+ binding and their Ca2+ binding affinity can be different from N-Cam. Consequently, here we address the charge state of the polar residues at these positions. The results show that the charge state of these polar residues can affect substantially the conformational change and the Ca2+ binding affinity of our N-Cam variants. Since all the variants kept their conformational activity in the presence of Ca2+ suggests that the differences observed among them mainly originate from the difference in their molecular dynamics. Hence we propose that the molecular dynamics of Ca2+ sensor EF-hand domains is a key factor in the multifunctional aspect of EF-hand proteins.
      Graphical abstract image

      PubDate: 2015-10-24T11:12:33Z
  • The C-terminal tail inhibitory phosphorylation sites of PTEN regulate its
           intrinsic catalytic activity and the kinetics of its binding to
    • Abstract: Publication date: 1 December 2015
      Source:Archives of Biochemistry and Biophysics, Volume 587
      Author(s): Yeong-Chit Joel Chia, Bruno Catimel, Daisy Sio Seng Lio, Ching-Seng Ang, Benjamin Peng, Hong Wu, Hong-Jian Zhu, Heung-Chin Cheng
      Dephosphorylation of four major C-terminal tail sites and occupancy of the phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]-binding site of PTEN cooperate to activate its phospholipid phosphatase activity and facilitate its recruitment to plasma membrane. Our investigation of the mechanism by which phosphorylation of these C-terminal sites controls the PI(4,5)P2-binding affinity and catalytic activity of PTEN resulted in the following findings. First, dephosphorylation of all four sites leads to full activation; and phosphorylation of any one site significantly reduces the intrinsic catalytic activity of PTEN. These findings suggest that coordinated inhibition of the upstream protein kinases and activation of the protein phosphatases targeting the four sites are needed to fully activate PTEN phosphatase activity. Second, PI(4,5)P2 cannot activate the phosphopeptide phosphatase activity of PTEN, suggesting that PI(4,5)P2 can only activate the phospholipid phosphatase activity but not the phosphoprotein phosphatase activity of PTEN. Third, dephosphorylation of all four sites significantly decreases the affinity of PTEN for PI(4,5)P2. Since PI(4,5)P2 is a major phospholipid co-localizing with the phospholipid- and phosphoprotein-substrates in plasma membrane, we hypothesise that the reduced affinity facilitates PTEN to “hop” on the plasma membrane to dephosphorylate these substrates.

      PubDate: 2015-10-24T11:12:33Z
  • TNFα triggers release of extracellular vesicles containing TNFR1 and
           TRADD, which can modulate TNFα responses of the parental cells
    • Abstract: Publication date: 1 December 2015
      Source:Archives of Biochemistry and Biophysics, Volume 587
      Author(s): Miwa Sohda, Yoshio Misumi, Kimimitsu Oda
      Tumor necrosis factor-α (TNFα)-induced reactions are effective to maintain homeostasis; however, excessive responses play progressive roles in the pathogenesis of various chronic inflammatory diseases. We demonstrate that TNFα triggered the release of its receptor TNFR1 as a content of extracellular vesicles (EVs) from the human bronchial epithelial cell, BEAS-2b. The TNFR1 cytoplasmic domain binding partner, TNFR-associated death domain (TRADD), was released by TNFα treatment along with TNFR1. TNFα-triggered release of EVs was decreased in the presence of amitriptyline, an inhibitor of acid sphingomyelinase (A-SMase), or of GW4869, an inhibitor of neutral sphingomyelinase (N-SMase), indicating that EVs containing TNFR1 and TRADD are released through A-SMase and N-SMase dependent manners. From sucrose density gradient analysis, each sphingomyelinase is involved in the generation of distinct populations of EVs. Inhibition of A-SMase or N-SMase resulted in significantly increased responses to TNFα in parental cells. Given that TRADD serves as a platform for the assembly of subsequent signaling molecules, the TNFα triggered release of TNFR1 and TRADD might be an effective strategy for down regulation of the TNFα responses of parental cells.

      PubDate: 2015-10-24T11:12:33Z
  • Homophilic interaction and deformation of E-cadherin and cadherin 7 probed
           by single molecule force spectroscopy
    • Abstract: Publication date: 1 December 2015
      Source:Archives of Biochemistry and Biophysics, Volume 587
      Author(s): Fei Wu, Prashant Kumar, Chen Lu, Ahmed El Marjou, Wu Qiu, Chwee Teck Lim, Jean Paul Thiery, Ruchuan Liu
      Cadherin-mediated adhesion plays a crucial role in multicellular organisms. Dysfunction within this adhesion system has major consequences in many pathologies, including cancer invasion and metastasis. However, mechanisms controlling cadherin recognition and adhesive strengthening are only partially understood. Here, we investigated the homophilic interactions and mechanical stability of the extracellular (EC) domains of E-cadherin and cadherin 7 using atomic force microscopy and magnetic tweezers. Besides exhibiting stronger interactions, E-cadherin also showed more efficient force-induced self-strengthening of interactions than cadherin 7. In addition, the distributions of the unbinding forces for both cadherins partially overlap with those of the unfolding forces, indicating that partial unfolding/deformation of the cadherin EC domains may take place during their homophilic interactions. These conformational changes may be involved in cadherins physiology function and contribute to the significant differences in adhesive strength mediated by type I and type II cadherins.

      PubDate: 2015-10-24T11:12:33Z
  • Early response as shown by enhancement of transglutaminase 1 expression
           after cisplatin-induced acute kidney injury
    • Abstract: Publication date: 15 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 586
      Author(s): Kentaro Furukawa, Miki Yamane, Hideki Tatsukawa, Kiyotaka Hitomi
      Acute kidney injury (AKI) is caused by drugs and other stimuli, which limits the use of several therapeutic approaches. The AKI mouse model generated by intraperitoneal administration with cisplatin, one of the most widely used anti-cancer drugs, is generally applied to study on this disease. Transglutaminases are posttranslational modifying enzymes that catalyze irreversible cross-linking reactions between proteins in several biological events such as skin formation and blood coagulation. In this study, we found an increase in the expression level of transglutaminase (TG1) in the kidney of mice which had been injected with cisplatin and underwent progressive nephrotoxicity. Before the appearance of the tentative symptoms of renal failure, which is apparent by morphological damage in the kidney and increases in blood creatinine levels, both the expression level and activity of TG1 rapidly increased mainly at the proximal tubule. On the other hand, the protein expression level of another major isozyme (TG2) remained mostly unaltered. This investigation will provide a possible basal-level biomarker and also information on progression of renal failure from the aspect of the protein-modifying enzyme, transglutaminase.

      PubDate: 2015-10-11T12:11:15Z
  • Specific role of taurine in the 8-brominated-2´-deoxyguanosine
    • Abstract: Publication date: Available online 9 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Takashi Asahi, Yoshimasa Nakamura, Yoji Kato, Toshihiko Osawa
      At the sites of inflammation, hypohalous acids, such as hypochlorous acid and hypobromous acid (HOBr), are produced by myeloperoxidase. These hypohalous acids rapidly react with the primary amino groups to produce haloamines, which are relatively stable and can diffuse long distances and cross the plasma membrane. In this study, we examined the effects of taurine, the most abundant free amino acid in the leukocyte cytosol, on the hypohalous acid-dependent formation of 8-chloro-2’-deoxyguanosine (8-CldG) and 8-bromo-2’-deoxyguanosine (8-BrdG). The reaction of taurine with HOBr yielded taurine bromamine, which is the most stable among other bromamines of α-amino acids. Taurine also enhanced the bromination of only dG among the four 2’-deoxynucleosides, whereas it inhibited the 8-CldG formation. The specificity of taurine for the enhanced formation of halogenated dG is completely different from that of nicotine, an enhancer of chlorination. The amount of dibrominated taurine (taurine dibromamine) closely correlated with the formation of 8-BrdG, suggesting that taurine dibromamine might be a plausible mediator for the dG bromination in vivo.
      Graphical abstract image

      PubDate: 2015-10-11T12:11:15Z
  • Temperature control of the motility of actin filaments interacting with
           myosin molecules using an electrically conductive glass in the presence of
           direct current
    • Abstract: Publication date: Available online 9 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Reito Wada, Daisuke Sato, Takao Nakamura, Kuniyuki Hatori
      The motility of actin filaments interacting with heavy meromyosin molecules was directly observed on indium tin oxide-coated glass (ITO-glass), over which a surface current flowed. Because the increase in surface current applied to ITO-glass increases the temperature, we focused on the temperature-dependence of the sliding velocity and the effect of the current flow on the orientation of filament motion. Using high precision fluorescence measurements, the displacement vectors of filaments were collected at intervals of 1/30 s. The direction of filament motion was independent to that of current flow up to 0.17 A (7.7 A/m of surface current density); however, the velocity increased by approximately 2-fold when the surface temperature increased from 25°C to 37°C. The moving actin filaments exhibited a broader velocity distribution at high temperature than at low temperature. Collectively, these data suggest that using ITO-glass with a surface current to generate a well-controlled temperature change may serve to evaluate temperature-dependent transient responses in protein activity under a microscope, without interference from electrical effects.

      PubDate: 2015-10-11T12:11:15Z
  • Identification of molecular determinants for the nuclear import of
           pseudorabies virus UL31
    • Abstract: Publication date: Available online 9 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Meili Li, Si Jiang, Chuncong Mo, Jinlin Wang, Jinlu Huang, Zhancheng Zeng, Xiaowei Li, Chunke Chen, Yanjia Yang, Tao Peng, Mingsheng Cai
      Herpes simplex virus 1 (HSV-1) UL31 is a multifunctional protein and important for HSV-1 infection. Pseudorabies virus (PRV) UL31 is a late protein homologous to HSV-1 UL31. Previous studies showed that PRV UL31 is predominantly localized to nucleus, however, the molecular determinants for its nuclear import were unclear to date. Here, by utilizing live cells fluorescent microscopy, UL31 fused with enhanced yellow fluorescent protein was transiently expressed in live cells and confirmed to exlusively target to the nucleus in the absence of other viral proteins. Furthermore, the nuclear import of UL31 was found to be dependent on the Ran-, importin α1-, α3-, α5-, α7-, β1-and transportin-1-mediated pathway. Therefore, these results would open up new avenues for depicting the biological functions of UL31 during PRV infection.

      PubDate: 2015-10-11T12:11:15Z
  • The members of M20D peptidase subfamily from Burkholderia cepacia,
           Deinococcus radiodurans and Staphylococcus aureus (HmrA) are
           carboxydipeptidases, primarily specific for Met-X dipeptides
    • Abstract: Publication date: Available online 9 October 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sahayog N. Jamdar, Venkata N. Are, Mallikarjunan Navamani, Saurabh Kumar, Vandan Nagar, Ravindra D. Makde
      Three members of peptidase family M20D from Burkholderia cepacia (BcepM20D; Uniprot accession no. A0A0F7GQ23), Deinococcus radiodurans R1 (DradM20D; Uniprot accession no. Q9RTP6) and Staphylococcus aureus (HmrA; Uniprot accession no. Q99Q45) were characterized in terms of their preference for various substrates. The results thus reveal that all the enzymes including HmrA lack endopeptidase as well as aminopeptidase activities and possess strong carboxypeptidase activity. Further, the amidohydrolase activity exerted on other substrates like N-Acetyl-Amino acids, N-Carbobenzoxyl-Amino acids and Indole acetic acid (IAA)-Amino acids is due to the ability of these enzymes to accommodate different types of chemical groups other than the amino acid at the S1 pocket. Further, data on peptide hydrolysis strongly suggests that all the three enzymes are primarily carboxydipeptidases exhibiting highest catalytic efficiency (k cat/K m 5-36 X 105 M-1 s-1) for Met-X substrates, where -X could be Ala/Gly/Ser/Tyr/Phe/Leu depending on the source organism. The supportive evidence for the substrate specificities was also provided with the molecular docking studies carried out using structure of SACOL0085 and homology modelled structure of BcepM20D. The preference for different substrates, their binding at active site of the enzyme and possible role of these enzymes in recycling of methionine are discussed in this study.

      PubDate: 2015-10-11T12:11:15Z
  • Mechanoreception at the cell membrane: More than the integrins
    • Abstract: Publication date: 15 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 586
      Author(s): Alexander N. Gasparski, Karen A. Beningo
      A cell receives mechanical cues from its surrounding microenvironment and transduces this mechanical information into a biochemical signal within the cell, ultimately resulting in physiological change. Several molecules within the plasma membrane have been identified that are capable of receiving and translating a mechanical signal. Although integrins are most often discussed as the cell's primary method of mechanoreception at the cell membrane, several non-integrin mechanoreceptors have emerged over the last decade. Specifically, multiple G-protein coupled receptors, the glycocalyx, ion channels, lipid rafts and receptor tyrosine kinases have been found to translate mechanical stimuli from the environment into cellular change. This review will discuss these non-integrin mechanoreceptors associated with the plasma membrane, and their impact on cell physiology.

      PubDate: 2015-10-06T22:08:00Z
  • PD150606 protects against ischemia/reperfusion injury by preventing
           μ-calpain-induced mitochondrial apoptosis
    • Abstract: Publication date: 15 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 586
      Author(s): Tao Luo, Rongchuan Yue, Houxiang Hu, Zhou Zhou, Kai Hang Yiu, Shuang Zhang, Lei Xu, Ke Li, Zhengping Yu
      Calpain plays an important role in myocardial ischemia/reperfusion (I/R) injury. PD150606, a nonpeptide, cell-permeable and noncompetitive calpain inhibitor, has been shown to have protective properties in ischemic disease. The aims of the present study were to investigate whether PD150606 could alleviate myocardial I/R injury and to examine the possible mechanisms involved. The I/R model was established in vivo in C57BL/6 mice and in vitro using neonatal mouse cardiomyocytes, respectively. To evaluate the protective effects of PD150606 on I/R injury, we measured the myocardial infarct area, apoptosis, and expression of cleaved caspase-3. We also investigated the underlying mechanisms by examining mitochondrial function as reflected by the ATP concentration, translocation of cytochrome c, dynamics of mPTP opening, and membrane potential (ΔΨm), coupled with calpain activity. Pretreatment with PD150606 significantly reduced the infarct area and apoptosis caused by I/R. PD150606 pretreatment also reduced mitochondrial dysfunction by inhibiting calpain activation. Moreover, we found that μ-calpain is the main contributor to I/R-induced calpain activation. Knockdown of μ-calpain with siRNA significantly reversed calpain activation, mitochondrial dysfunction, and cardiomyocyte apoptosis caused by I/R in vitro. Our results suggest that PD150606 may protect against I/R injury via preventing μ-calpain-induced mitochondrial apoptosis.

      PubDate: 2015-10-03T13:53:08Z
  • Glutathione modifies the oxidation products of 2’-deoxyguanosine by
           singlet molecular oxygen
    • Abstract: Publication date: Available online 30 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Patrícia S. Peres, Andressa Valerio, Silvia M.S.C. Cadena, Sheila M.B. Winnischofer, Alexsandra C. Scalfo, Paolo Di Mascio, Glaucia R. Martinez
      The oxidation of the free nucleoside 2’-deoxyguanosine (dGuo) by singlet molecular oxygen (1O2) has been studied over the three last decades due to the major role of DNA oxidation products in process such as ageing, mutation and carcinogenesis. In the present work we investigated the dGuo oxidation by 1O2 in the presence of the important low molecular antioxidant, glutathione, in its reduced (GSH) and oxidized (GSSG) forms. There were applied different conditions of concentration, pH, time of incubation, and the use of a [18O]-labeled thermolabile endoperoxide naphthalene derivative as a source of [18O]-labeled 1O2. Data was obtained through high performance liquid chromatography (HPLC) and HPLC coupled to micrOTOFQ-II analysis of the main oxidation products: the diastereomers of spiroiminodihydantoin-2′-deoxyribonucleosides (dSp) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo). An intriguing result was that 8-oxodGuo levels increased by 100 fold when dGuo was oxidized by 1O2 in the presence of GSH and by 2 fold in the presence of GSSG, while dSp levels dropped to zero for both conditions. All data from dGuo, 8-oxodGuo and dSp quantification together with the analysis of residual GSH/GSSG content in each sample strongly suggest that glutathione modifies the mechanism of dGuo oxidation by 1O2 by disfavoring the pathway of dSp formation.

      PubDate: 2015-10-03T13:53:08Z
  • Functional structure and physiological functions of mammalian wild-type
    • Abstract: Publication date: Available online 30 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Tomoya Okamoto, Ryuichi Ishida, Hiroshi Yamamoto, Masako Tanabe-Ishida, Asami Haga, Hiroki Takahashi, Kyosuke Takahashi, Daisuke Goto, Ewa Grave, Hideaki Itoh
      The Chaperonins comprise a family of molecular chaperones having a double-ring structure and similar sequence homology. These proteins play an essential role in biological reactions that mediate the folding of newly synthesized polypeptides and partially denatured proteins. In the prokaryotic group I chaperonins, structural and reaction cycle analyses of GroEL and its co-chaperone GroES have been performed in detail. While in eukaryotes, there have been limited reports analying the group I chaperonin HSP60 and its co-chaperone HSP10. In the present study, we purified the wild type HSP60 from porcine liver and investigated the interaction between HSP60 and HSP10, including conformation and physiological relationships. Based on the results of transmission electron microscopy, native PAGE, and gel filtration column chromatography, the wild type HSP60 displayed a heptameric single-ring structure in the absence of ATP. In contrast, HSP60 formed mainly a “football-type” complex with HSP10 in the presence of ATP and mediated the refolding of denatured substrate protein. The functional conformation cycle of the purified mammalian HSP60 is distinct from the cycle of the prokaryotic GroEL/GroES chaperonin.

      PubDate: 2015-10-03T13:53:08Z
  • Insulin treatment promotes tyrosine phosphorylation of PKR and inhibits
           polyIC induced PKR threonine phosphorylation
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Medchalmi Swetha, Kolluru V.A. Ramaiah
      Tyrosine phosphorylation of insulin receptor beta (IRβ) in insulin treated HepG2 cells is inversely correlated to ser51 phosphorylation in the alpha-subunit of eukaryotic initiation factor 2 (eIF2α) that regulates protein synthesis. Insulin stimulates interaction between IRβ and PKR, double stranded RNA-dependent protein kinase, also known as EIF2AK2, and phosphorylation of tyrosine residues in PKR, as analyzed by immunoprecipitation and pull down assays using anti-IRβ and anti-phosphotyrosine antibodies, recombinant IRβ and immunopurified PKR. Further polyIC or synthetic double stranded RNA-induced threonine phosphorylation or activation of immunopurified and cellular PKR is suppressed in the presence of insulin treated purified IRβ and cell extracts. Acute, but not chronic, insulin treatment enhances tyrosine phosphorylation of IRβ, its interaction with PKR and tyrosine phosphorylation of PKR. In contrast, lipopolysaccharide that stimulates threonine phosphorylation of PKR and eIF2α phosphorylation and AG 1024, an inhibitor of the tyrosine kinase activity of IRβ, reduces PKR association with the receptor, IRβ in HepG2 cells. These findings therefore may suggest that tyrosine phosphorylated PKR plays a role in the regulation of insulin induced protein synthesis and in maintaining insulin sensitivity, whereas, suppression of polyIC-mediated threonine phosphorylation of PKR by insulin compromises its ability to fight against virus infection in host cells.
      Graphical abstract image

      PubDate: 2015-09-29T13:46:23Z
  • The structural basis of substrate promiscuity in UDP-hexose
           4-epimerase from the hyperthermophilic Eubacterium Thermotoga
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Sun-Mi Shin, Jin Myung Choi, Eric di Luccio, Yong-Jik Lee, Sang-Jae Lee, Sang Jun Lee, Sung Haeng Lee, Dong-Woo Lee
      UDP-galactose 4-epimerase (GalE) catalyzes the interconversion of UDP-glucose (UDP-Glc) and UDP-galactose (UDP-Gal), which is a pivotal step in the Leloir pathway for d-galactose metabolism. Although GalE is widely distributed in prokaryotes and eukaryotes, little information is available regarding hyperthermophilic GalE. We overexpressed the TM0509 gene, encoding a putative GalE from Thermotoga maritima (TMGalE), in Escherichia coli and characterized the encoded protein. To further investigate the molecular basis of this enzyme's catalytic function, we determined the crystal structures of TMGalE and TMGalE bound to UDP-Glc at resolutions of 1.9 Å and 2.0 Å, respectively. The enzyme was determined to be a homodimer with a molecular mass of 70 kDa. The enzyme could reversibly catalyze the epimerization of UDP-GalNAc/UDP-GlcNAc as well as UDP-Gal/UDP-Glc at elevated temperatures, with an apparent optimal temperature and pH of 80 °C and 7.0, respectively. Our data showed that TM0509 is a UDP-galactosugar 4-epimerase involved in d-galactose metabolism; consequently, this study provides the first detailed characterization of a hyperthermophilic GalE. Moreover, the promiscuous substrate specificity of TMGalE, which is more similar to human GalE than E. coli GalE, supports the notion that TMGalE might exhibit the earliest form of sugar-epimerizing enzymes in the evolution of galactose metabolism.
      Graphical abstract image

      PubDate: 2015-09-25T13:44:26Z
  • Crystal structure and tartrate inhibition of Legionella pneumophila
           histidine acid phosphatase
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Richa Dhatwalia, Harkewal Singh, Thomas J. Reilly, John J. Tanner
      Histidine acid phosphatases (HAPs) utilize a nucleophilic histidine residue to catalyze the transfer of a phosphoryl group from phosphomonoesters to water. HAPs function as protein phosphatases and pain suppressors in mammals, are essential for Giardia lamblia excystation, and contribute to virulence of the category A pathogen Francisella tularensis. Herein we report the first crystal structure and steady-state kinetics measurements of the HAP from Legionella pneumophila (LpHAP), also known as Legionella major acid phosphatase. The structure of LpHAP complexed with the inhibitor l(+)-tartrate was determined at 2.0 Å resolution. Kinetics assays show that l(+)-tartrate is a 50-fold more potent inhibitor of LpHAP than of other HAPs. Electrostatic potential calculations provide insight into the basis for the enhanced tartrate potency: the tartrate pocket of LpHAP is more positive than other HAPs because of the absence of an ion pair partner for the second Arg of the conserved RHGXRXP HAP signature sequence. The structure also reveals that LpHAP has an atypically expansive active site entrance and lacks the nucleotide substrate base clamp found in other HAPs. These features imply that nucleoside monophosphates may not be preferred substrates. Kinetics measurements confirm that AMP is a relatively inefficient in vitro substrate of LpHAP.
      Graphical abstract image

      PubDate: 2015-09-25T13:44:26Z
  • Understanding of real alternative redox partner of Streptomyces peucetius
           DoxA: Prediction and validation using in silico and in vitro analyses
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Hemraj Rimal, Seung-Won Lee, Joo-Ho Lee, Tae-Jin Oh
      Streptomyces peucetius ATCC27952 contains the cytochrome P450 monoxygenase DoxA that is responsible for the hydroxylation of daunorubicin into doxorubicin. Although S. peucetius ATCC27952 contains several potential redox partners, the most suitable endogenous electron-transport system is still unclear; therefore, we conducted a study of potential redox partners using Accelrys Discovery Studio 3.5. Recombinant DoxA along with its redox partners from S. peucetius FDX1, FDR2, and FDX3, and the putidaredoxin and putidaredoxin reductase from Pseudomonas putida that are essential equivalents of the class I type of bacterial electron-transport system were over-expressed and purified. The successful development of an efficient redox system was achieved by an in vitro enzymatic catalysis reaction with DoxA. The optimal pH for the activation of the heme was 7.6 and the optimal temperature was 30 °C. Our findings suggest a two-fold increase of DoxA activity via the NADH → FDR2 → FDX1 → DoxA pathway for the hydroxylation of the daunorubicin, and indicate that the usage of a native redox partner may increase daunorubicin-derived doxorubicin production due to the inclusion of DoxA.

      PubDate: 2015-09-25T13:44:26Z
  • Enhanced heme accessibility in horse heart mini-myoglobin: Insights from
           molecular modelling and reactivity studies
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Fabio Polticelli, Veranika Zobnina, Chiara Ciaccio, Giampiero de Sanctis, Paolo Ascenzi, Massimo Coletta
      Mini-myoglobin (mini-HHMb) is a fragment of horse-heart myoglobin (HHMb) considered to be the prototype of the product encoded by the central exon of the HHMb gene. For this reason, mini-HHMb has been studied extensively showing that carbonylation and oxygenation properties of the ferrous form are similar to those of the full-length protein, while kinetics and thermodynamics of azide binding to the ferric form are significantly different from those of HHMb. To analyze the structure–function relationships in mini-HHMb and the role of conformational fluctuations in ligand accessibility, the molecular model of mini-HHMb has been built and refined by molecular dynamics simulations, and analyzed in parallel with that of full length HHMb. Moreover, imidazole binding parameters of ferric mini-HHMb and HHMb have been determined. Furthermore, structural data of ferric mini-HHMb and HHMb have been correlated with the imidazole and previously determined azide binding properties. Present results indicate that, despite the extensive trimming, the heme-α-helices E-F substructure is essentially unaltered in mini-HHMb with respect to HHMb. However, the heme-Fe atom displays an enhanced accessibility in mini-HHMb, which may affect both ligand association and dissociation kinetics.
      Graphical abstract image

      PubDate: 2015-09-21T13:31:13Z
  • Phosphatidylglycerol-Derived Phospholipids Have a Universal,
           Domain-Crossing Role in Stress Responses
    • Abstract: Publication date: Available online 21 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Luis Alberto Luévano-Martínez, Alicia J. Kowaltowski
      Phosphatidylglycerol and phospholipids derived from it are widely distributed throughout the three domains of life. Cardiolipin is the best characterized of these phospholipids, and plays a key role in the response to environmental variations. Phosphatidylglycerol-derived phospholipids confer cell membranes with a wide range of responses, including changes in surface charge, fluidity, flexibility, morphology, biosynthesis and remodeling, that adapt the cell to these situations. Furthermore, the synthesis and remodeling of these phospholipids is finely regulated, highlighting the importance of these lipids in cell homeostasis and responses during stressful situations. In this article, we review the most important roles of these anionic phospholipids across domains, focusing on the biophysical basis by which these phospholipids are used in stress responses.
      Graphical abstract image

      PubDate: 2015-09-21T13:31:13Z
  • Relationship between calcium mobilization and platelet α- and
           δ-granule secretion. A role for TRPC6 in thrombin-evoked
           δ-granule exocytosis
    • Abstract: Publication date: Available online 18 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): E. Lopez, N. Bermejo, A. Berna-Erro, N. Alonso, G.M. Salido, P.C. Redondo, J.A. Rosado
      Changes in cytosolic Ca2+ concentration ([Ca2+]c) regulate granule secretion in different cell types. Thrombin activates PAR1 and PAR4 receptors and promotes release of Ca2+ from distinct intracellular stores, which, in turn, activates store-operated Ca2+ entry (SOCE). A crucial step during platelet function is the release of physiological agonists stored in secretory granules to the extracellular compartment during activation. We aim to study the role of Ca2+ mobilization from the extracellular compartment or from different intracellular stores in platelet granule secretion. By using flow cytometry, we have found that α- and δ-granules are secreted in thrombin-stimulated platelets in the absence of extracellular Ca2+, and in a concentration-dependent manner. Our findings show that thrombin-stimulated granule secretion depends on Ca2+ mobilization from intracellular stores. Analysis of the kinetics of granule secretion reveals that platelet stimulation with thrombin results in rapid release of α-granules which precedes the secretion of δ-granules. Incubation of platelets with a specific antibody, which recognizes the extracellular amino acid sequence 573-586 of TRPC6, inhibited thrombin-evoked δ-granule exocytosis. Our results indicate that the mechanisms underlying thrombin-induced α- and δ-granule secretion show differences in dependency on Ca2+ mobilization.

      PubDate: 2015-09-21T13:31:13Z
  • Regulation of Ca2+/calmodulin-dependent protein kinase phosphatase
           (CaMKP/PPM1F) by protocadherin-γC5 (Pcdh-γC5)
    • Abstract: Publication date: Available online 18 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Takashi Onouchi, Yoshimi Kishino-Kaneko, Isamu Kameshita, Atsuhiko Ishida, Noriyuki Sueyoshi
      Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP/PPM1F) is a Ser/Thr protein phosphatase that belongs to the PPM family. It is important to identify an endogenous regulator of CaMKP. Using an Escherichia coli two-hybrid screening method, we identified the C-terminal cytoplasmic fragment of protocadherin γ subfamily C5 (Pcdh-γC5), which was generated by intracellular processing, as a CaMKP-binding protein. Dephosphorylation of phosphorylated Ca2+/calmodulin-dependent protein kinase I (CaMKI) by CaMKP was significantly activated by the C-terminal cytoplasmic fragment, Pcdh-γC5(715-944), both in vitro and in cells, suggesting that the C-terminal fragment functions as an endogenous activator of CaMKP. The nuclear translocation of the fragment was blocked by its binding to cytoplasmic CaMKP to form a ternary complex with CaMKI. Taken together, these results strongly suggest that the C-terminal cytoplasmic fragment of Pcdh-γC5 acts as a scaffold for CaMKP and CaMKI to regulate CaMKP activity. These findings may provide new insights into the reversible regulation of CaMKP in cells.

      PubDate: 2015-09-21T13:31:13Z
  • Selective antagonization of activated Nrf2 and inhibition of cancer cell
           proliferation by procyanidins from Cinnamomi Cortex extract
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Tomokazu Ohnuma, Eri Anzai, Yohei Suzuki, Mai Shimoda, Shin Saito, Takahito Nishiyama, Kenichiro Ogura, Akira Hiratsuka
      Nuclear factor-E2-related factor 2 (Nrf2) is an important transcription factor and plays a central role in inducible expression of many cytoprotective genes. Recent studies have reported that various cancer cells having unrestrained Nrf2 due to its overexpression exhibit increased proliferation and resistance to chemotherapy. Suppression of abnormal Nrf2 activation is needed for a new therapeutic approach against these cancers. Our previous study found that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells. In the present study, we investigated the effect of CCE procyanidins on Nrf2 activity and cell proliferation in several cancer cells, which have normal or constitutively active Nrf2. Interestingly, CCE procyanidin treatment selectively reduced Nrf2 expression and inhibited cell proliferation in cancer cells that overexpress Nrf2, but these phenomena were not seen in cells with low Nrf2 expression. Moreover, transfection assay demonstrated that CCE procyanidins had selective inhibition of activated Nrf2. These results suggest that CCE procyanidins might be an effective cancer therapeutic agent to selectively suppress abnormal Nrf2 activation responsible for enhanced proliferation.

      PubDate: 2015-09-21T13:31:13Z
  • Bisphenol A stimulates the epithelial mesenchymal transition of estrogen
           negative breast cancer cells via FOXA1 signals
    • Abstract: Publication date: 1 November 2015
      Source:Archives of Biochemistry and Biophysics, Volume 585
      Author(s): Xiao-Lin Zhang, Hong-Sheng Wang, Na Liu, Li-Chen Ge
      Estrogen receptor negative (ER-) breast cancer are associated with increased risks for metastasis and high rates of recurrence. Our present study revealed that nanomolar bisphenol A (BPA), a typical endocrine disrupting chemical, promoted the in vitro migration and induced mesenchymal transition (EMT) of ER-breast cancer cells. PCR array revealed that BPA can down regulate 12 and up regulate 2 genes involved in regulation of signal transduction and biological pathways of breast cancer. The down regulated genes included FOXA1, which is a key determinant of endocrine response and down regulated by BPA via a time dependent manner. Silencing of FOXA1 by siRNA triggered the EMT of SkBr3 cells. While over expression of FOXA1 abolished BPA induced EMT. Further, 10−8 M BPA significantly increased the phosphorylation of ERK1/2, p38-MAPK, and Akt in SkBr3 cells, while only PI3K/Akt inhibitor LY294002 attenuated the BPA induced down regulation of FOXA1 and E-Cadherin (E-Cad). Over expression of Akt also suppressed FOXA1 expression in SkBr3 cells. It suggested that PI3K/Akt mediated, at least partially, BPA induced EMT of ER-breast cancer cells. In summary, our data provided the first evidence that BPA can promote the EMT of ER-breast cancer cells through down regulation of FOXA1.

      PubDate: 2015-09-21T13:31:13Z
  • Interaction of the chlorite-based drug WF10 and chlorite with hemoglobin,
           methemoglobin and ferryl hemoglobin
    • Abstract: Publication date: Available online 21 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Annelie Pichert, Jürgen Arnhold
      The interaction of the chlorite-based drug solution WF10 with human oxyhemoglobin and oxidized hemoglobin forms was investigated monitoring the corresponding spectral changes in heme states. The chlorite component of WF10 converts oxyhemoglobin into methemoglobin with a rate of 35.4 M-1s-1. Methemoglobin is also formed upon the interaction of ferryl hemoglobin and WF10/chlorite. The rate of this interconversion depends on the oxidation state of ferryl hemoglobin. This rate is 114 M-1s-1, when ferryl hemoglobin was generated upon reaction of oxyhemoglobin and hydrogen peroxide. A considerable higher rate (6600 M-1s-1) is measured between the chlorite components of WF10 and ferryl hemoglobin after formation of the latter species from methemoglobin. WF10/chlorite inactivates also methemoglobin as evidenced by the continuous decrease of the Soret band and all other absorbances with a rate of 8.3 M-1s-1. In all interconversions, the chlorite component of WF10 was the active principle as shown in experiments applying pure chlorite at the same concentration as in WF10. Thus, WF10 is able to diminish efficiently the yield of cytotoxic hemoglobin species that might appear after excessive hemolysis of red blood cells under pathologic situations.
      Graphical abstract image

      PubDate: 2015-09-21T13:31:13Z
  • Analysis of the pH-Dependent Stability and Millisecond Folding Kinetics of
           Horse Cytochrome c
    • Abstract: Publication date: Available online 16 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rishu Jain, Rajesh Kumar, Sandeep Kumar, Ritika Chhabra, Mukesh Chand Agarwal, Rajesh Kumar
      This paper analyzes the effect of pH on thermodynamic stability and folding kinetics of horse cytochrome c (cyt c). Analysis of equilibrium unfolding transitions of Ferricyt c and Ferrocyt c measured between pH 3.0 and pH 13.0 reveal that these proteins have maximum thermodynamic stability between pH 8.0 and pH 9.5. Theoretically predicted pH-dependent electrostatic unfolding energy of Ferricyt c also supports this result. Unfolded Ferrocyt c in refolding buffer at pH 7.0 and pH 12.7 refolds rapidly to native state. Between pH 7.0 and pH 12.7, the activation free energy barrier for folding of Ferrocyt c varies by <1.0 kcal mol-1 while the folding free energy, which is measured by two-state analysis of equilibrium unfolding transitions of Ferrocyt c varies by 8.0 kcal mol-1. This finding reveals that the large disparity in thermodynamic stability between pH 7.0 and pH 12.7 is not strongly reflected in the refolding rates. The Wyman Tanford linkage relation was used to calculate the βpH-value for folding of Ferrocyt c, which is <0.1 between pH 7.0 and pH 12.7, indicating that the electrostatic interactions are weakly formed in transition state and exhibit a very small effect on the folding kinetics.
      Graphical abstract image

      PubDate: 2015-09-17T13:19:09Z
  • Blue Copper Proteins: A rigid machine for efficient electron transfer, a
           flexible device for metal uptake
    • Abstract: Publication date: 15 October 2015
      Source:Archives of Biochemistry and Biophysics, Volume 584
      Author(s): Sergio Alejo Pérez-Henarejos, Luis A. Alcaraz, Antonio Donaire
      Blue Copper Proteins (BCPs) are small and generally soluble copper-containing proteins which participate in monoelectron transfer processes in biological systems. An overview of their electronic and tertiary structure is detailed here. The well-established entatic/rack-induced mechanism is explained by comparing thermodynamic parameters between the folded (tense) and the unfolded (relaxed) forms of the BCP rusticyanin. Recently, NMR solution data have shown that the active sites of BCPs in absence of the metal ion, i.e. in the apoforms, are flexible in the micro-to-second timescale. The rigidity proposed by the entatic/rack-induced mechanism is an imperative for the holoprotein to perform electron transfer; while the flexibility of the apocupredoxin is necessary to uptake the metal ion from the metallochaperones. These apparently contradictory requirements are discussed in the present work. Finally, the role of azurin and some peptides derived from it in anticancer therapy are also described.
      Graphical abstract image

      PubDate: 2015-09-17T13:19:09Z
  • Contribution to catalysis of ornithine binding residues in ornithine
    • Abstract: Publication date: Available online 12 September 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Reeder Robinson, Insaf A. Qureshi, Catherine A. Klancher, Pedro J. Rodriguez, John J. Tanner, Pablo Sobrado
      The SidA ornithine N5-monooxygenase from A. fumigatus is a flavin monooxygenase that catalyzes the NADPH-dependent hydroxylation of ornithine. Herein we report a mutagenesis study targeting four residues that contact ornithine in crystal structures of SidA: Lys107, Asn293, Asn323, and Ser469. Mutation of Lys107 to Ala abolishes activity as measured in steady-state oxygen consumption and ornithine hydroxylation assays, indicating that the ionic interaction of Lys107 with the carboxylate of ornithine is essential for catalysis. Mutation of Asn293, Asn323, or Ser469 individually to Ala results in >14-fold increases in Km values for ornithine. Asn323 to Ala also increases the rate constant for flavin reduction by NADPH by 18-fold. Asn323 is unique among the four ornithine binding residues in that it also interacts with NADPH by forming a hydrogen bond with the nicotinamide ribose. The crystal structure of N323A complexed with NADP+ and ornithine shows that the nicontinamide riboside group of NADP+ is disordered. This result suggests that the increase in flavin reduction rate results from an increase in conformational space available to the enzyme-bound NADP(H). Asn323 thus facilitates ornithine binding at the expense of hindering flavin reduction, which demonstrates the delicate balance that exists within protein-ligand interaction networks in enzyme active sites.
      Graphical abstract image

      PubDate: 2015-09-13T13:13:37Z
  • Microbial oxidative stress response: Novel insights from environmental
           facultative anaerobic bacteria
    • Abstract: Publication date: 15 October 2015
      Source:Archives of Biochemistry and Biophysics, Volume 584
      Author(s): Huihui Fu, Jie Yuan, Haichun Gao
      Facultative bacteria can grow under either oxic or anoxic conditions. While oxygen provides substantial advantages in energy yield by respiration, it can become life-threatening because of reactive oxygen species that derive from the molecule naturally. Thus, to survive and thrive in a given niche, these bacteria have to constantly regulate physiological processes to make maximum benefits from oxygen respiration while restraining oxidative stress. Molecular mechanisms and physiological consequences of oxidative stress have been under extensive investigation for decades, mostly on research model Escherichia coli, from which our understanding of bacterial oxidative stress response is largely derived. Nevertheless, given that bacteria live in enormously diverse environments, to cope with oxidative stress different strategies are conceivably developed.

      PubDate: 2015-09-04T13:05:29Z
  • Key roles of Tyr 10 in Cu bound Aβ complexes and its relevance to
           Alzheimer's disease
    • Abstract: Publication date: 15 October 2015
      Source:Archives of Biochemistry and Biophysics, Volume 584
      Author(s): Naihao Lu, Jiayu Li, Zhonghong Gao
      Recent studies show that the accumulation of redox-active Cu mediates the aggregation of amyloid β-peptide (Aβ) and conspicuous oxidative damage to the brain in Alzheimer's disease (AD). However, the key roles for Tyr 10 in Aβ–Cu(II) complex and its potential biological relevance to AD etiology under oxidative stress, were not stressed enough. Interestingly, our results indicated that Aβ40 (not Aβ16)–Cu(II) complex showed obviously enhanced peroxidase activity than free Cu(II). Although Tyr 10 was not the residue binding Cu(II), the mutation of Tyr 10 residue in Aβ40 decreased the peroxidase activity of Aβ40–Cu(II) complex, and the mutation of Tyr 10 could inhibit Aβ40 aggregation. Under oxidative and nitrative stress conditions, the Aβ–Cu(II) complex caused oxidation and nitration of the Aβ Tyr 10 residue through peroxidase-like reactions, where the formation of Cu(I) and hydroxyl radical (OH) was proposed as a chemical mechanism. We also showed that, when Aβ40 aggregates were bound to Cu(II), they retained peroxidase-like activity. Therefore, Tyr 10 residue is pivotal in Aβ–Cu(II) complex and shows important relevance to oxidative stress, implicating the novel significance of Tyr 10 residue as well as Aβ–Cu(II) complex in the pathology of AD.

      PubDate: 2015-08-31T13:54:55Z
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