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BIOCHEMISTRY (217 journals)                  1 2 3     

AAPS PharmSciTech     Hybrid Journal   (Followers: 7)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Central Science     Hybrid Journal  
ACS Chemical Biology     Full-text available via subscription   (Followers: 158)
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: 6)
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: 10)
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: 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: 72)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 11)
American Journal of Polymer Science     Open Access   (Followers: 22)
Amino Acids     Hybrid Journal   (Followers: 6)
Analytical Biochemistry     Hybrid Journal   (Followers: 74)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 37)
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: 4)
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: 159)
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: 9)
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: 5)
Biochimie     Hybrid Journal   (Followers: 5)
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 15)
BioDrugs     Full-text available via subscription   (Followers: 9)
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Biofuels     Hybrid Journal   (Followers: 11)
Biogeochemistry     Hybrid Journal   (Followers: 10)
BioInorganic Reaction Mechanisms     Hybrid Journal   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 12)
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: 23)
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: 5)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 4)
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: 3)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 19)
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: 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: 5)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 2)

        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]
  • Glutamate cysteine ligase and the age-related decline in cellular
           glutathione: the therapeutic potential of γ-glutamylcysteine
    • Abstract: Publication date: Available online 2 February 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Gavin Ferguson, Wallace Bridge
      A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide γ-glutamylcysteine (γ-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous γ-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases.
      Graphical abstract image

      PubDate: 2016-02-02T11:34:38Z
  • Role of dietary flavonoids in amelioration of sugar induced
    • Abstract: Publication date: Available online 30 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kapil K. Patil, Rohan J. Meshram, Nagesh A. Dhole, Rajesh N. Gacche
      Sugar induced cataractogenesis and visual impairment is more prominent ophthalmic problem in humans suffering from diabetes. Flavonoids have been identified as one of the therapeutically important class of phytochemicals possessing myriad of biological activities. Analysing the anti-cataract effects of flavonoids from natural sources is an important aspect owing to their bioavailability in variety of dietary sources. In the present study a panel of ten dietary flavonoids like 3, 6-dihydroxy flavone, 3, 7-dihydroxy flavone, chrysin, 3-hydroxy-7-methoxy flavone, apigenin, genistein, baicalein, galangin, Biochanin-A, and diosmin were evaluated for their anti-cataract effects in sugar induced lens model studies. Series of parameters like role of flavonoids in glycation induced lens opacity, protein aggregation measurements, carbonyl group formation: a biochemical marker of glycation reaction, non-tryptophan fluorescence: a marker of formation of advanced glycation end products (AGEs) and assessment of (experimental and in silico) aldose reductase inhibition: a key enzyme of polyol pathway involved in cataractogenesis. The results of the study clearly demonstrated the impressive anti-cataract activity of chrysin followed by significant activity by apigenin, baicalein and genistein. The results of the present study may find applications in formulation of functional foods and neutraceuticals for the management of diabetic cataract.
      Graphical abstract image

      PubDate: 2016-02-02T11:34:38Z
  • Properties and catalytic activities of MICAL1, the flavoenzyme involved in
           cytoskeleton dynamics, and modulation by its CH, LIM and C-terminal
    • Abstract: Publication date: Available online 1 February 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Teresa Vitali, Elisa Maffioli, Gabriella Tedeschi, Maria A. Vanoni
      MICAL1 is a cytoplasmic 119 kDa protein participating in cytoskeleton dynamics through the NADPH-dependent oxidase and F-actin depolymerizing activities of its N-terminal flavoprotein domain, which is followed by calponin homology (CH), LIM domains and a C-terminal region with Pro-, Glu-rich and coiled-coil motifs. MICAL1 and truncated forms lacking the C-terminal, LIM and/or CH regions have been produced and characterized. The CH, LIM and C-terminal regions cause an increase of Km,NADPH exhibited by the NADPH oxidase activity of the flavoprotein domain, paralleling changes in the overall protein charge. The C-terminus also determines a ∼10-fold decrease of kcat, revealing its role in establishing an inactive/active conformational equilibrium, which is at the heart of the regulation of MICAL1 in cells. F-actin lowers Km,NADPH (10-50 μM) and increases kcat (10-25 s-1) to similar values for all MICAL forms. The apparent Km,actin of MICAL1 is ∼10-fold higher than that of the other forms (3-5 μM), reflecting the fact that F-actin binds to flavoprotein domain in the MICAL’s active conformation and stabilizes it. Analyses of the reaction in the presence of F-actin indicate that actin depolymerization is mediated by H2O2 produced by the NADPH oxidase reaction, rather than due to direct hydroxylation of actin methionine residues.

      PubDate: 2016-02-02T11:34:38Z
  • Cell survival of glioblastoma grown in medium containing hydrogen peroxide
           and/or nitrite, or in plasma-activated medium
    • Abstract: Publication date: Available online 26 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Naoyuki Kurake, Hiromasa Tanaka, Kenji Ishikawa, Takashi Kondo, Makoto Sekine, Kae Nakamura, Hiroaki Kajiyama, Fumitaka Kikkawa, Masaaki Mizuno, Masaru Hori
      Non-equilibrium atmospheric pressure plasmas generate a high electron density (on the order of 1016 electrons per cm−3) using Ar gas. Culture medium in air at room temperature was plasma-irradiated for several hundred seconds. Tens of micromolar hydrogen peroxide (H2O2) and millimolar levels of nitrous ion (NO2 −) were detected in the plasma-irradiated culture medium (plasma activated medium; PAM) and selectively induced the apoptotic death of glioblastoma tumor cells, but did not kill normal mammary epithelial cells. A similar antitumor effect was induced by spiking the medium with comparable concentrations of H2O2 and NO2 −. The PAM remained still a somewhat difference that it should also be assessed for understanding other latent mechanisms.
      Graphical abstract image

      PubDate: 2016-01-28T11:23:12Z
  • Galectin expression in healing wounded skin treated with low-temperature
           plasma: comparison with treatment by electronical coagulation
    • Abstract: Publication date: Available online 28 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yoshihiro Akimoto, Sanae Ikehara, Takashi Yamaguchi, Jaeho Kim, Hayato Kawakami, Nobuyuki Shimizu, Masaru Hori, Hajime Sakakita, Yuzuru Ikehara
      Low-temperature plasma is useful for the care of wounded skin. It accelerates wound healing. However, the mechanism of this effect has not been fully elucidated yet. Galectin-1 is reported to accelerate wound healing via the Smad signaling pathway. In the present study to clarify whether or not galectins were expressed during the process of wound healing in the plasma-treated skin, we examined the effect of low-temperature plasma on galectin expression in the healing skin. We compared the effects of low-temperature plasma on the expression of galectin-1, -2, and -3 in the healing skin with those of electrocoagulation conducted with a high-frequency electrical coagulator. Immediately after the start of low-temperature plasma treatment following the incision made in the skin, a membrane-like structure was formed on the surface of the wound. Immunoelectron microscopy showed that these galectins were localized in the membrane-like structure of the plasma-treated skin. The expressions of these galectins were increased by the low-temperature plasma treatment, whereas they were inhibited by the electrocoagulation. These results suggest that galectins were involved in the wound healing of low-temperature plasma-treated skin. Galectins will thus be good markers for further examination of the effects of low-temperature plasma on the healing of wounded skin.

      PubDate: 2016-01-28T11:23:12Z
  • Tanshinone IIA affects the HDL subfractions distribution not serum lipid
           levels: Involving in intake and efflux of cholesterol
    • Abstract: Publication date: Available online 26 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Lian-qun Jia, Ni Zhang, Ying Xu, Wen-na Chen, Mei-lin Zhu, Nan Song, Lu Ren, Hui-min Cao, Jun-yan Wang, Guan-lin Yang
      Aim of study Tanshinone IIA is an active component of the traditional Chinese medicine. This study aimed at investigating the mechanism of tanshinone IIA on anti-atherosclerosis, which may be because of that Tanshinone IIA can affect the HDL subfractions distribution and then regulate reverse cholesterol transport. Materials and methods A model of hyperlipidaemia in rats was used. Tanshinone IIA was given daily after hyperlipidaemia. In vivo, lipid deposition and morphological changes in liver were analyzed; HDL subfractions and lipid level in serum as well as in liver were measured; the expression of genes related to cholesterol intake in liver and peritoneal macrophage cholesterol efflux were evaluated. In vitro, HepG2 cells and THP-1 cells were pretreated with tanshinone IIA and subsequently with ox-LDL to evaluate the total cholesterol and the expression of related genes. Results Tanshinone IIA reduced the lipid deposition in liver. Moreover, it did not affect the serum lipid levels but reduced the levels of HDL middle subfractions and increased the levels of HDL large subfractions. Furthermore, tanshinone IIA could regulate the expressions of CYP7A1, LDL-R, SREBP2 and LCAT in the liver as well as the ABCA1 and CD36 in macrophage cells which is involving in the cholesterol intake and efflux respectively. It could reduce lipid accumulation caused by ox-LDL induction, and that also regulate the expressions of LDL-R, HMGCR and SREBP2 in HepG2 and ABCA1, CD36 in THP-1 cells. Conclusion A novel finding that tanshinone IIA was not reduce the serum lipid level but affects the HDL subfractions distribution and thereby regulating the intake and efflux of cholesterol.

      PubDate: 2016-01-28T11:23:12Z
  • Intracellular trafficking of the pyridoxal cofactor. Implications for
           health and metabolic disease
    • Abstract: Publication date: 15 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 592
      Author(s): James W. Whittaker
      The importance of the vitamin B6-derived pyridoxal cofactor for human health has been established through more than 70 years of intensive biochemical research, revealing its fundamental roles in metabolism. B6 deficiency, resulting from nutritional limitation or impaired uptake from dietary sources, is associated with epilepsy, neuromuscular disease and neurodegeneration. Hereditary disorders of B6 processing are also known, and genetic defects in pathways involved in transport of B6 into the cell and its transformation to the pyridoxal-5’-phosphate enzyme cofactor can contribute to cardiovascular disease by interfering with homocysteine metabolism and the biosynthesis of vasomodulatory polyamines. Compared to the processes involved in cellular uptake and processing of the B6 vitamers, trafficking of the PLP cofactor across intracellular membranes is very poorly understood, even though the availability of PLP within subcellular compartments (particularly the mitochondrion) may have important health implications. The aim of this review is to concisely summarize the state of current knowledge of intracellular trafficking of PLP and to identify key directions for future research.

      PubDate: 2016-01-21T17:54:10Z
  • Synthesis, Delivery and Regulation of Eukaryotic Heme and Fe-S Cluster
    • Abstract: Publication date: Available online 16 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Dulmini P. Barupala, Stephen P. Dzul, Pamela Jo Riggs-Gelasco, Timothy L. Stemmler
      In humans, the bulk of iron in the body (over 75%) is directed towards heme- or Fe-S cluster cofactor synthesis, and the complex, highly regulated pathways in place to accomplish biosynthesis have evolved to safely assemble and load these cofactors into apoprotein partners. In eukaryotes, heme biosynthesis is both initiated and finalized within the mitochondria, while cellular Fe-S cluster assembly is controlled by correlated pathways both within the mitochondria and within the cytosol. Iron plays a vital role in a wide array of metabolic processes and defects in iron cofactor assembly leads to human diseases. This review describes progress towards our molecular-level understanding of cellular heme and Fe-S cluster biosynthesis, focusing on the regulation and mechanistic details that are essential for understanding human disorders related to the breakdown in these essential pathways.

      PubDate: 2016-01-17T17:52:07Z
  • Functional importance of αIle-346 and αIle-348 in the catalytic
           sites of Escherichia coli ATP synthase
    • Abstract: Publication date: Available online 14 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Chao Zhao, Hiba Syed, Sherif S. Hassan, Vineet K. Singh, Zulfiqar Ahmad
      We studied the functional role of highly conserved VISIT-DG sequence residues αIle-346 and αIle-348 in the catalytic sites of Escherichia coli F1Fo ATP synthase. αIle-346 is in close proximity, 2.98 and 3.63 Å, to the two known phosphate binding residues αR376 and βR182; αIle-348 is situated within 3.66 Å from βR182. Single or double mutants of both αI346 and αI348 resulted in a variable loss of oxidative phosphorylation and ATPase activity. Azide, fluoroaluminate, and fluoroscandium caused insignificant to significant inhibition of mutants. Whereas the wild-type enzyme was completely inhibited by NBD-Cl (7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole), a variable extent of inhibition was observed for αI346 and αI348 mutants. MgPi protection against NBD-Cl induced inhibition of wild-type, αI346, and αI348 demonstrated that, although strongly conserved, αI346 and αI348 have no direct role in phosphate binding. Insertion of Arginine in the form of αI346R/βR182A, αI346R/αR376A, or αI348R/βR182A was able to compensate for the absence of known phosphate-binding Arginine residues βR182 and αR376. Results also suggest that αIle-346 and αIle-348 seem to have functional importance in upholding the phosphate-binding subdomain and transition state stabilization in the catalytic sites of E. coli ATP synthase.

      PubDate: 2016-01-17T17:52:07Z
  • The A31P missense mutation in cardiac myosin binding protein C alters
           protein structure but does not cause haploinsufficiency
    • Abstract: Publication date: Available online 9 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sabine J. van Dijk, Kristina Bezold Kooiker, Stacy Mazzalupo, Yuanzhang Yang, Alla S. Kostyukova, Debbie J. Mustacich, Elaine R. Hoye, Joshua A. Stern, Mark D. Kittleson, Samantha P. Harris
      Mutations in MYBPC3, the gene encoding cardiac myosin binding protein C (cMyBP-C), are a major cause of hypertrophic cardiomyopathy (HCM). While most mutations encode premature stop codons, missense mutations causing single amino acid substitutions are also common. Here we investigated effects of a single proline for alanine substitution at amino acid 31 (A31P) in the C0 domain of cMyBP-C, which was identified as a natural cause of HCM in cats. Results using recombinant proteins showed that the mutation disrupted C0 structure, altered sensitivity to trypsin digestion, and reduced recognition by an antibody that preferentially recognizes N-terminal domains of cMyBP-C. Western blots detecting A31P cMyBP-C in myocardium of cats heterozygous for the mutation showed a reduced amount of A31P mutant protein relative to wild-type cMyBP-C, but the total amount of cMyBP-C was not different in myocardium from cats with or without the A31P mutation indicating altered rates of synthesis/degradation of A31P cMyBP-C. Also, the mutant A31P cMyBP-C was properly localized in cardiac sarcomeres. These results indicate that reduced protein expression (haploinsufficiency) cannot account for effects of the A31P cMyBP-C mutation and instead suggest that the A31P mutation causes HCM through a poison polypeptide mechanism that disrupts cMyBP-C or myocyte function.

      PubDate: 2016-01-13T23:42:28Z
  • The drug binding sites and transport mechanism of the RND pumps from
           Mycobacterium tuberculosis: insights from Molecular Dynamics simulations
    • Abstract: Publication date: Available online 12 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Padmani Sandhu, Yusuf Akhter
      RND permease superfamily drug efflux pumps are involved in the multidrug transport and are attractive to study them for therapeutic purpose. In previous work we have classified 14 members of MmpL proteins from Mycobacterium tuberculosis (Mtb) within its families [Sandhu P and Akhter Y, 2015. Int J Med Microbiol., 305:413-23]. In this study, structures of these proteins were homology modelled. The drug binding sites and channels were identified using local micro-stereochemistry and charge densities within these proteins. Potential transport mechanism based on differential structural behaviour in the absence and on the binding of drug molecules was explained using the molecular dynamics simulations results. Our studies showed two potential drug binding sites positioned at opposite ends of the transport tunnel leading from cytoplasmic to the periplasmic space across MmpL5 trimer. The drug binding have effects on the structural conformation of the protein leading to molecular-scale peristaltic movements. The free binding energy calculations reveal that the subsequent binding events are interdependent and may have implications on transport mechanism. Two drug binding sites and a continuous channel in the RND pump have been reported. The proposed ligand binding mechanism showed peristaltic movements in the channel leading to the drug efflux. This study would be helpful in understanding the molecular basis of drugs resistance in Mtb.
      Graphical abstract image

      PubDate: 2016-01-13T23:42:28Z
  • Computational Crystallization
    • Abstract: Publication date: Available online 11 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Irem Altan, Patrick Charbonneau, Edward H. Snell
      Crystallization is a key step in macromolecular structure determination by crystallography. While a robust theoretical treatment of the process is available, due to the complexity of the system, the experimental process is still largely one of trial and error. In this article, efforts in the field are discussed together with a theoretical underpinning using a solubility phase diagram. Prior knowledge has been used to develop tools that computationally predict the crystallization outcome and define mutational approaches that enhance the likelihood of crystallization. For the most part these tools are based on binary outcomes (crystal or no crystal), and the full information contained in an assembly of crystallization screening experiments is lost. The potential of this additional information is illustrated by examples where new biological knowledge can be obtained and where a target can be sub-categorized to predict which class of reagents provides the crystallization driving force. Computational analysis of crystallization requires complete and correctly formatted data. While massive crystallization screening efforts are under way, the data available from many of these studies are sparse. The potential for this data and the steps needed to realize this potential are discussed.
      Graphical abstract image

      PubDate: 2016-01-13T23:42:28Z
  • The Effect of Cardiomyopathy Mutation (R97L) in Mouse Cardiac Troponin T
           on the Muscle Length-mediated Recruitment of Crossbridges is Modified
           Divergently by α- and β-myosin Heavy Chain
    • Abstract: Publication date: Available online 11 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sampath K. Gollapudi, Murali Chandra
      Hypertrophic cardiomyopathy mutations in cardiac troponin T (TnT) lead to sudden cardiac death. Augmented myofilament Ca2+ sensitivity is a common feature in TnT mutants, but such observations fail to provide a rational explanation for severe cardiac phenotypes. To better understand the mutation-induced effect on the cardiac phenotype, it is imperative to determine the effects on dynamic contractile features such as the muscle length (ML)-mediated activation against α- and β-myosin heavy chain (MHC) isoforms. α- and β-MHC are not only differentially expressed in rodent and human hearts, but they also modify ML-mediated activation differently. Mouse analog of human TnTR94L (TnTR97L) or wild-type TnT was reconstituted into de-membranated muscle fibers from normal (α-MHC) and transgenic (β-MHC) mouse hearts. TnTR97L augmented myofilament Ca2+ sensitivity by a similar amount in α- and β-MHC fibers. However, TnTR97L augmented the negative impact of strained crossbridges on other crossbridges (γ) by 22% in α-MHC fibers, but attenuated γ by 21% in β-MHC fibers. TnTR97L decreased the magnitude of ML-mediated recruitment of crossbridges (E R) by 37% in α-MHC fibers, but increased E R by 35% in β-MHC fibers. We provide a mechanistic basis for the TnTR97L-induced effects in α- and β-MHC fibers and discuss the relevance to human hearts.

      PubDate: 2016-01-13T23:42:28Z
  • Kv1.3 potassium channel mediates macrophage migration in atherosclerosis
           by regulating ERK activity
    • Abstract: Publication date: 1 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 591
      Author(s): Xiao-Hong Kan, Hai-Qing Gao, Zhi-Yong Ma, Lin Liu, Ming-Ying Ling, Yuan-Yuan Wang
      Ion channels expressed in macrophages have been tightly related to atherosclerosis by coupling cellular function. How the voltage-gated potassium channels (Kv) affect macrophage migration remain unknown. The aim of our study is to investigate whether Kv1.3-ERK signaling pathway plays an important role in the process. We explored the expression of Kv1.3 in coronary atherosclerotic heart disease and found Kv1.3 channel was increased in acute coronary syndrome patients. Treatment of RAW264.7 cells with Kv1.3 small interfering RNA, suppressed cell migration. The expression of phosphorylated ERK1/2 also decreased after knockdown of Kv1.3. On the other hand, overexpression of Kv1.3 channel promoted cell migration and ERK1/2 phosphorylation. U-0126, the mitogen-activated protein kinase inhibitors, could reverse macrophage migration induced by Kv1.3 channel overexpression. Downregulation of Kv1.3 channel by siRNA could not further inhibit cell migration when cells were treated with U-0126. It means that ERK is downstream signal of Kv1.3 channel. We concluded that Kv1.3 may stimulate macrophage migration through the activation of ERK.

      PubDate: 2016-01-13T23:42:28Z
  • The xanthophyll cycle pigments, violaxanthin and zeaxanthin, modulate
           molecular organization of the photosynthetic antenna complex LHCII
    • Abstract: Publication date: Available online 8 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ewa Janik, Joanna Bednarska, Monika Zubik, Karol Sowinski, Rafal Luchowski, Wojciech Grudzinski, Dariusz Matosiuk, Wieslaw I. Gruszecki
      The effect of violaxanthin and zeaxanthin, two main carotenoids of the xanthophyll cycle, on molecular organization of LHCII, the principal photosynthetic antenna complex of plants, was studied in a model system based on lipid-protein membranes, by means of analysis of 77 K chlorophyll a fluorescence and “native” electrophoresis. Violaxanthin was found to promote trimeric organization of LHCII, contrary to zeaxanthin which was found to destabilize trimeric structures. Moreover, violaxanthin was found to induce decomposition of oligomeric LHCII structures formed in the lipid phase and characterized by the fluorescence emission band at 715 nm. Both pigments promoted formation of two-component supramolecular structures of LHCII and xanthophylls. The violaxanthin-stabilized structures were composed mostly of LHCII trimers while, the zeaxanthin-stabilized supramolecular structures of LHCII showed more complex organization which depended periodically on the xanthophyll content. The effect of the xanthophyll cycle pigments on molecular organization of LHCII was analyzed based on the results of molecular modeling and discussed in terms of a physiological meaning of this mechanism. Supramolecular structures of LHCII stabilized by violaxanthin, prevent uncontrolled oligomerization of LHCII, potentially leading to excitation quenching, therefore can be considered as structures protecting the photosynthetic apparatus against energy loses at low light intensities.
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      PubDate: 2016-01-08T23:25:22Z
  • Physical basis for the ofloxacin-induced acceleration of lysozyme
           aggregation and polymorphism in amyloid fibrils
    • Abstract: Publication date: Available online 8 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Shivani A. Muthu, Nivin Mothi, Sonali M. Shiriskar, Raghuvir R.S. Pissurlenkar, Anil Kumar, Basir Ahmad
      Aggregation of globular proteins is an intractable problem which generally originates from partially folded structures. The partially folded structures first collapse non-specifically and then reorganize into amyloid-like fibrils via one or more oligomeric intermediates. The fibrils and their on/off pathway intermediates may be toxic to cells and form toxic deposits in different human organs. To understand the basis of origins of the aggregation diseases, it is vital to study in details the conformational properties of the amyloidogenic partially folded structures of the protein. In this work, we examined the effects of ofloxacin, a synthetic fluoroquinolone compound on the fibrillar aggregation of hen egg-white lysozyme. Using two aggregation conditions (4M GuHCl at pH 7.0 and 37 °C; and pH 1.7 at 65 °C) and a number of biophysical techniques, we illustrate that ofloxacin accelerates fibril formation of lysozyme by binding to partially folded structures and modulating their secondary, tertiary structures and surface hydrophobicity. We also demonstrate that Ofloxacin-induced fibrils show polymorphism of morphology, tinctorial properties and hydrophobic surface exposure. This study will assist in understanding the determinant of fibril formation and it also indicates that caution should be exercised in the use of ofloxacin in patients susceptible to various aggregation diseases.
      Graphical abstract image

      PubDate: 2016-01-08T23:25:22Z
  • ERβ up-regulation was involved in silibinin-induced growth inhibition
           of human breast cancer MCF-7 cells
    • Abstract: Publication date: Available online 6 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Nan Zheng, Lu Liu, Weiwei Liu, Ping Zhang, Huai Huang, Linghe Zang, Toshihiko Hayashi, Shin-ichi Tashiro, Satoshi Onodera, Mingyu Xia, Takashi Ikejima
      We previously reported that silibinin induced a loss of cell viability in breast cancer (MCF-7) cells by ERα down-regulation. But whether this cytotoxicity depends on another estrogen receptor, ERβ, has yet to be elucidated. Therefore, we sought to explore the effects of ERβ modulation on cell viability by using an ERβ-selective agonist (Diarylprepionitrile, DPN) and an antagonist (PHTPP). Our data demonstrated that ERβ served as a growth suppressor in MCF-7 cells, and the incubation of silibinin, elevated ERβ expression, resulting in the tumor growth inhibition. The cytotoxic effect of silibinin was diminished by PHTPP and enhanced by DPN. Silencing of ERβ by siRNA confirmed these results. Apoptotic cascades, including the sequential activation of caspase-9 and -6, and finally the cleavage of caspase substrates, PARP and ICAD, caused by treatment with silibinin, were all repressed by PHTPP pre-treatment but exacerbated by DPN. Unlike ERα, ERβ did not involve autophagic process in the regulation, since neither autophagic inhibitor (3-MA) nor the inducer (rapamycin) affected the cell survival rates regardless ERβ activity. Taken together, silibinin induced apoptosis through mitochondrial pathway by up-regulating ERβ pathways in MCF-7 cells without the involvement of autophagy.

      PubDate: 2016-01-08T23:25:22Z
  • Effects of myosin light chain phosphorylation on length-dependent myosin
           kinetics in skinned rat myocardium
    • Abstract: Publication date: Available online 5 January 2016
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hannah C. Pulcastro, Peter O. Awinda, Jason J. Breithaupt, Bertrand C.W. Tanner
      Myosin force production is Ca2+-regulated by thin-filament proteins and sarcomere length, which together determine the number of cross-bridge interactions throughout a heartbeat. Ventricular myosin regulatory light chain-2 (RLC) binds to the neck of myosin and modulates contraction via its phosphorylation state. Previous studies reported regional variations in RLC phosphorylation across the left ventricle wall, suggesting that RLC phosphorylation could alter myosin behavior throughout the heart. We found that RLC phosphorylation varied across the left ventricle wall and that RLC phosphorylation was greater in the right vs. left ventricle. We also assessed functional consequences of RLC phosphorylation on Ca2+-regulated contractility as sarcomere length varied in skinned rat papillary muscle strips. Increases in RLC phosphorylation and sarcomere length both led to increased Ca2+-sensitivity of the force-pCa relationship, and both slowed cross-bridge detachment rate. RLC-phosphorylation slowed cross-bridge rates of MgADP release (∼30%) and MgATP binding (∼50%) at 1.9 μm sarcomere length, whereas RLC phosphorylation only slowed cross-bridge MgATP binding rate (∼55%) at 2.2 μm sarcomere length. These findings suggest that RLC phosphorylation influences cross-bridge kinetics differently as sarcomere length varies and support the idea that RLC phosphorylation could vary throughout the heart to meet different contractile demands between the left and right ventricles.

      PubDate: 2016-01-08T23:25:22Z
  • The role of endothelial mechanosensitive genes in atherosclerosis
           and omics approaches
    • Abstract: Publication date: 1 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 591
      Author(s): Rachel D. Simmons, Sandeep Kumar, Hanjoong Jo
      Atherosclerosis is the leading cause of morbidity and mortality in the U.S., and is a multifactorial disease that preferentially occurs in regions of the arterial tree exposed to disturbed blood flow. The detailed mechanisms by which d-flow induces atherosclerosis involve changes in the expression of genes, epigenetic patterns, and metabolites of multiple vascular cells, especially endothelial cells. This review presents an overview of endothelial mechanobiology and its relation to the pathogenesis of atherosclerosis with special reference to the anatomy of the artery and the underlying fluid mechanics, followed by a discussion of a variety of experimental models to study the role of fluid mechanics and atherosclerosis. Various in vitro and in vivo models to study the role of flow in endothelial biology and pathobiology are discussed in this review. Furthermore, strategies used for the global profiling of the genome, transcriptome, miR-nome, DNA methylome, and metabolome, as they are important to define the biological and pathophysiological mechanisms of atherosclerosis. These “omics” approaches, especially those which derive data based on a single animal model, provide unprecedented opportunities to not only better understand the pathophysiology of atherosclerosis development in a holistic and integrative manner, but also to identify novel molecular and diagnostic targets.
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      PubDate: 2016-01-04T23:03:01Z
  • The anticancer potential of steroidal saponin, dioscin, isolated from wild
           yam (Dioscorea villosa) root extract in invasive human breast cancer cell
           line MDA-MB-231 in vitro
    • Abstract: Publication date: 1 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 591
      Author(s): Pranapda Aumsuwan, Shabana I. Khan, Ikhlas A. Khan, Zulfiqar Ali, Bharathi Avula, Larry A. Walker, Zia Shariat-Madar, William G. Helferich, Benita S. Katzenellenbogen, Asok K. Dasmahapatra
      Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to find out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast cancer cells. MCF-7 and MDA-MB-231 cells were treated in the absence/presence of various concentrations of DS and subjected to gene analysis by RT-qPCR, immunoblotting, and immunocytochemistry. We determined the ability of MDA-MB-231 cells to migrate into wound area and examined the effects of DS on cellular invasion using invasion assay. DS reduced cell viability of both cell lines in a concentration and time-dependent manner. GATA3 expression was enhanced by DS (5.76 μM) in MDA-MB-231 cells. DS (5.76 μM)-treated MDA-MB-231 cells exhibited the morphological characteristic of epithelial-like cells; mRNA expression of DNMT3A, TET2, TET3, ZFPM2 and E-cad were increased while TET1, VIM and MMP9 were decreased. Cellular invasion of MDA-MB-231 was reduced by 65 ± 5% in the presence of 5.76 μM DS. Our data suggested that DS-mediated pathway could promote GATA3 expression at transcription and translation levels. We propose that DS has potential to be used as an anti-invasive agent in breast cancer.

      PubDate: 2015-12-31T22:03:28Z
  • Mechanistic implications from structures of yeast alcohol dehydrogenase
           complexed with coenzyme and an alcohol
    • Abstract: Publication date: 1 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 591
      Author(s): Bryce V. Plapp, Henry A. Charlier, S. Ramaswamy
      Yeast alcohol dehydrogenase I is a homotetramer of subunits with 347 amino acid residues, catalyzing the oxidation of alcohols using NAD+ as coenzyme. A new X-ray structure was determined at 3.0 Å where both subunits of an asymmetric dimer bind coenzyme and trifluoroethanol. The tetramer is a pair of back-to-back dimers. Subunit A has a closed conformation and can represent a Michaelis complex with an appropriate geometry for hydride transfer between coenzyme and alcohol, with the oxygen of 2,2,2-trifluoroethanol ligated at 2.1 Å to the catalytic zinc in the classical tetrahedral coordination with Cys-43, Cys-153, and His-66. Subunit B has an open conformation, and the coenzyme interacts with amino acid residues from the coenzyme binding domain, but not with residues from the catalytic domain. Coenzyme appears to bind to and dissociate from the open conformation. The catalytic zinc in subunit B has an alternative, inverted coordination with Cys-43, Cys-153, His-66 and the carboxylate of Glu-67, while the oxygen of trifluoroethanol is 3.5 Å from the zinc. Subunit B may represent an intermediate in the mechanism after coenzyme and alcohol bind and before the conformation changes to the closed form and the alcohol oxygen binds to the zinc and displaces Glu-67.

      PubDate: 2015-12-31T22:03:28Z
  • Transbilayer asymmetry and sphingomyelin composition modulate the
           preferential membrane partitioning of the nicotinic acetylcholine receptor
           in Lo domains
    • Abstract: Publication date: 1 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 591
      Author(s): Vanesa L. Perillo, Daniel A. Peñalva, Alejandro J. Vitale, Francisco J. Barrantes, Silvia S. Antollini
      We have previously shown that the intact nicotinic acetylcholine receptor (AChR) lacks preference for Lo domains when reconstituted in a sphingomyelin (SM), cholesterol (Chol) and POPC (1:1:1) model system (Bermúdez V, Antollini SS, Fernández-Nievas GA, Aveldaño MI, Barrantes FJ. J. Lipid Res. 2010; 51: 2629–2641). Here, we have furthered our studies by characterizing the influence of different lipid host compositions on the distribution of purified AChR reconstituted in two model systems (POPC:Chol, 1:1 and POPC:Chol:SM, 1:1:1), involving a) different SM species (porcine brain SM (bSM), 16:0-SM, 18:0-SM or 24:1-SM); or b) induced transbilayer asymmetry, resulting from enrichment in bSM in the external hemilayer. AChR distribution was evaluated by fluorescence resonance energy transfer efficiency between the AChR intrinsic fluorescence and Laurdan or dehydroergosterol fluorescence, and by analyzing the distribution of AChR in detergent-resistant and detergent-soluble fractions (1% Triton X-100, 4 °C). bSM-induced transbilayer asymmetry or the presence of 16:0-SM and/or 18:0-SM (unlike bSM or 24:1-SM) resulted in the preferential partitioning of AChR in Lo domains, suggesting that the localization of AChR in ordered domains strongly depends on the characteristics of the host lipid membrane, and in particular on the sphingolipid composition and transbilayer asymmetry.
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      PubDate: 2015-12-31T22:03:28Z
  • Keap1/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic
           and lipogenic program in mice on a high-fat diet
    • Abstract: Publication date: 1 February 2016
      Source:Archives of Biochemistry and Biophysics, Volume 591
      Author(s): Stephen L. Slocum, John J. Skoko, Nobunao Wakabayashi, Susan Aja, Masayuki Yamamoto, Thomas W. Kensler, Dionysios V. Chartoumpekis
      The Keap1/Nrf2 pathway, known to regulate the expression of a series of cytoprotective and antioxidant genes, has been studied in the context of obesity and type 2 diabetes; diseases that are characterized by chronic oxidative stress. There is increasing evidence, however, that the transcription factor Nrf2 can crosstalk with pathways not directly related to cytoprotection. Our present work focuses on the effect of Nrf2 on hepatic gluconeogenesis and lipogenesis, two metabolic processes which are dysregulated in the obese/diabetic state. To this end, a genetic mouse model of Nrf2 pathway activation was used (Keap1-hypo; both Keap1 alleles are hypomorphic) and was exposed to a 3-month high-fat diet along with the relevant control wild-type mice. The Keap1-hypo mice were partially protected from obesity, had lower fasting glucose and insulin levels and developed less liver steatosis compared to the wild-type. Key gluconeogenic and lipogenic enzymes were repressed in the Keap1-hypo livers with concomitant activated Ampk signaling. Primary Keap1-hypo hepatocyte cultures also show increased Ampk signaling and repressed glucose production. In conclusion, increased Keap1/Nrf2 signaling in the liver is accompanied by repressed gluconeogenesis and lipogenesis that can, at least partially, explain the ameliorated diabetic phenotype in the Keap1-hypo mice.
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      PubDate: 2015-12-31T22:03:28Z
  • Mammalian proteasome subtypes: their diversity in structure and function
    • Abstract: Publication date: Available online 25 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Burkhardt Dahlmann
      The 20S proteasome is a multicatalytic proteinase catalysing the degradation of the majority of intracellular proteins. Thereby it is involved in almost all basic cellular processes, which is facilitated by its association with various regulator complexes so that it appears in different disguises like 26S proteasome, hybrid-proteasome and others. The 20S proteasome has a cylindrical structure built up by four stacked rings composed of α- and β-subunits. Since the three active site-containing β-subunits can all or in part be replaced by immuno-subunits, three main subpopulations exist, namely standard-, immuno- and intermediate-proteasomes. Due to posttranslational modifications or/and genetic variations all α- and β-subunits occur in multiple iso- or proteoforms. This leads to the fact that each of the three subpopulations is composed of a variety of 20S proteasome subtypes. This review summarizes the knowledge of proteasome subtypes in mammalian cells and tissues and their possible biological and medical relevancy.

      PubDate: 2015-12-27T21:26:38Z
  • N-terminal arm of orchardgrass Hsp17.2 (DgHsp17.2) is essential for both
           in vitro chaperone activity and in vivo thermotolerance in yeast
    • Abstract: Publication date: Available online 24 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Joon-Yung Cha, Sang-Hoon Lee, Kyung Hye Seo, Young Jin Choi, Mi Sun Cheong, Daeyoung Son
      Small heat shock proteins are well-known to function as chaperone in the protection of proteins and subcellular structures against stress-induced denaturation in many cell compartments. Irrespective of such general functional assignment, a proof of function in a living organism is missing. Here, we used heat-induced orchardgrass small Hsp17.2 (DgHsp17.2). Its function in in vitro chaperone properties has shown in protecting the model substrate, malate dehydrogenase (MDH) and citrate synthase (CS). Overexpression of DgHsp17.2 triggering strong chaperone activity enhanced in vivo thermotolerance of yeast cells. To identify the functional domain on DgHsp17.2 and correlationship between in vitro chaperone property and in vivo thermotolerance, we generated truncation mutants of DgHsp17.2 and showed essentiality of the N-terminal arm of DgHsp17.2 for the chaperone function. In addition, beyond for acquisition of thermotolerance irrespective of sequences are diverse among the small Hsps. However, any truncation mutants of DgHsp17.2 did not exhibit strong interaction with orchardgrass heat shock protein 70 (DgHsp70) different from mature DgHsp17.2, indicating that full-length DgHsp17.2 is necessary for cooperating with Hsp70 protein. Our study indicates that the N-terminal arm of DgHsp17.2 is an important region for chaperone activity and thermotolerance.

      PubDate: 2015-12-27T21:26:38Z
  • Guest Editorial: Special issue on metabolomics
    • Abstract: Publication date: 1 January 2016
      Source:Archives of Biochemistry and Biophysics, Volume 589
      Author(s): Marc-Emmanuel Dumas, Jerzy Adamski, Karsten Suhre

      PubDate: 2015-12-23T20:57:44Z
  • Recent developments in sample preparation and data pre-treatment in
           metabonomics research
    • Abstract: Publication date: 1 January 2016
      Source:Archives of Biochemistry and Biophysics, Volume 589
      Author(s): Ning Li, Yi peng Song, Huiru Tang, Yulan Wang
      Metabonomics is a powerful approach for biomarker discovery and an effective tool for pinpointing endpoint metabolic effects of external stimuli, such as pathogens and disease development. Due to its wide applications, metabonomics is required to deal with various biological samples of different properties. Hence sample preparation and corresponding data pre-treatment become important factors in ensuring validity of an investigation. In this review, we summarize some recent developments in metabonomics sample preparation and data-pretreatment procedures.

      PubDate: 2015-12-23T20:57:44Z
  • Quality assurance in the pre-analytical phase of human urine samples by 1H
           NMR spectroscopy
    • Abstract: Publication date: 1 January 2016
      Source:Archives of Biochemistry and Biophysics, Volume 589
      Author(s): Kathrin Budde, Ömer-Necmi Gök, Maik Pietzner, Christine Meisinger, Michael Leitzmann, Matthias Nauck, Anna Köttgen, Nele Friedrich
      Metabolomic approaches investigate changes in metabolite profiles, which may reflect changes in metabolic pathways and provide information correlated with a specific biological process or pathophysiology. High-resolution 1H NMR spectroscopy is used to identify metabolites in biofluids and tissue samples qualitatively and quantitatively. This pre-analytical study evaluated the effects of storage time and temperature on 1H NMR spectra from human urine in two settings. Firstly, to evaluate short time effects probably due to acute delay in sample handling and secondly, the effect of prolonged storage up to one month to find markers of sample miss-handling. A number of statistical procedures were used to assess the differences between samples stored under different conditions, including Projection to Latent Structure Discriminant Analysis (PLS-DA), non-parametric testing as well as mixed effect linear regression analysis. The results indicate that human urine samples can be stored at 10 °C for 24 h or at −80 °C for 1 month, as no relevant changes in 1H NMR fingerprints were observed during these time periods and temperature conditions. However, some metabolites most likely of microbial origin showed alterations during prolonged storage but without facilitating classification. In conclusion, the presented protocol for urine sample handling and semi-automatic metabolite quantification is suitable for large-scale epidemiological studies.

      PubDate: 2015-12-23T20:57:44Z
  • Epoxide hydrolase-catalyzed enantioselective conversion of trans-stilbene
           oxide: Insights into the reaction mechanism from steady-state and
           pre-steady-state enzyme kinetics
    • Abstract: Publication date: Available online 20 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Alain Archelas, Wei Zhao, Bruno Faure, Gilles Iacazio, Michael Kotik
      A detailed kinetic study based on steady-state and pre-steady-state measurements is described for the highly enantioselective epoxide hydrolase Kau2. The enzyme, which is a member of the α/β-hydrolase fold family, preferentially reacts with the (S,S)-enantiomer of trans-stilbene oxide (TSO) with an E value of ∼200. The enzyme follows a classical two-step catalytic mechanism with formation of an alkyl-enzyme intermediate in the first step and hydrolysis of this intermediate in a rate-limiting second step. Tryptophan fluorescence quenching during TSO conversion appears to correlate with alkylation of the enzyme. The steady-state data are consistent with (S,S) and (R,R)-TSO being two competing substrates with marked differences in k cat and K M values. The high enantiopreference of the epoxide hydrolase is best explained by pronounced differences in the second-order alkylation rate constant (k 2/K S) and the alkyl-enzyme hydrolysis rate k 3 between the (S,S) and (R,R)-enantiomers of TSO. Our data suggest that during conversion of (S,S)-TSO the two active site tyrosines, Tyr157 and Tyr259, serve mainly as electrophilic catalysts in the alkylation half-reaction, polarizing the oxirane oxygen of the bound epoxide through hydrogen bond formation, however, without fully donating their hydrogens to the forming alkyl-enzyme intermediate.
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      PubDate: 2015-12-23T20:57:44Z
  • Binding of human myeloperoxidase to red blood cells: molecular targets and
           biophysical consequences at the plasma membrane level
    • Abstract: Publication date: Available online 20 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Irina V. Gorudko, Alexey V. Sokolov, Ekaterina V. Shamova, Daria V. Grigorieva, Elena V. Mironova, Igor V. Kudryavtsev, Sergey A. Gusev, Alexander A. Gusev, Andrey V. Chekanov, Vadim B. Vasilyev, Sergey N. Cherenkevich, Oleg M. Panasenko, Alexander V. Timoshenko
      Myeloperoxidase (MPO) is an oxidant-producing enzyme that can also bind to cellular surface proteins. We found that band 3 protein and glycophorins A and B were the key MPO-binding targets of human red blood cells (RBCs). The interaction of MPO with RBC proteins was mostly electrostatic in nature because it was inhibited by desialation, exogenic sialic acid, high ionic strength, and extreme pH. In addition, MPO failed to interfere with the lectin-induced agglutination of RBCs, suggesting a minor role of glycan-recognizing mechanisms in MPO binding. Multiple biophysical properties of RBCs were altered in the presence of native (i.e., not hypochlorous acid-damaged) MPO. These changes included transmembrane potential, availability of intracellular Ca2+, and lipid organization in the plasma membrane. MPO-treated erythrocytes became larger in size, structurally more rigid, and hypersensitive to acidic and osmotic hemolysis. Furthermore, we found a significant correlation between the plasma MPO concentration and RBC rigidity index in type-2 diabetes patients with coronary heart disease. These findings suggest that MPO functions as a mediator of novel regulatory mechanism in microcirculation, indicating the influence of MPO-induced abnormalities on RBC deformability under pathological stress conditions.
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      PubDate: 2015-12-23T20:57:44Z
  • Ursodeoxycholic and deoxycholic acids: differential effects on intestinal
           Ca2+ uptake, apoptosis and autophagy of rat intestine
    • Abstract: Publication date: Available online 18 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Valeria A. Rodríguez, María A. Rivoira, Adriana del V. Pérez, Ana M. Marchionatti, Nori G. Tolosa de Talamoni
      The aim of this work was to study the effect of sodium deoxycholate (NaDOC) and ursodeoxycholic acid (UDCA) on Ca2+ uptake by enterocytes and the underlying mechanisms. Rats were divided into four groups: a) controls, b) treated with NaDOC, c) treated with UDCA d) treated with NaDOC and UDCA. Ca2+ uptake was studied in enterocytes with different degrees of maturation. Apoptosis, autophagy and NO content and iNOS protein expression were evaluated. NaDOC decreased and UDCA increased Ca2+ uptake only in mature enterocytes. The enhancement of protein expression of Fas, FasL, caspase-8 and caspase-3 activity by NaDOC indicates triggering of the apoptotic extrinsic pathway, which was blocked by UDCA. NO content and iNOS protein expression were enhanced by NaDOC, and avoided by UDCA. The increment of acidic vesicular organelles and LC3 II produced by NaDOC was also prevented by UDCA. In conclusion, the inhibitory effects of NaDOC on intestinal Ca2+ absorption occur by decreasing the Ca2+ uptake by mature enterocytes. NaDOC triggers apoptosis and autophagy, in part as a result of nitrosative stress. In contrast, UDCA increases the Ca2+ uptake by mature enterocytes, and in combination with NaDOC acts as an antiapoptotic and antiautophagic agent normalizing the transcellular Ca2+ pathway.

      PubDate: 2015-12-20T04:27:07Z
  • MEF2C orthologues from zebrafish: evolution, expression and promoter
    • Abstract: Publication date: Available online 17 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Andreia Adrião, Natércia Conceição, M. Leonor Cancela
      MEF2C is a crucial transcription factor for cranial neural crest cells development. An abnormal expression of this protein leads to severe abnormalities in craniofacial features. Recently, a human disease (MRD20) was described as a consequence of MEF2C haploinsufficiency. These patients show severe developmental delay, intellectual disability and dysmorphic features. Zebrafish presents two MEF2C orthologues, mef2ca and mef2cb. In this study we demonstrate a highly conserved pattern of chromosome localization for MEF2C between human and zebrafish, a similar protein sequence and tissue expression profile. We have focused our functional analysis on the zebrafish orthologue mef2cb. We identified three new exons through 5' RACE and described two new transcriptional start sites (TSS). These alternative TSS reflect the occurrence of two alternative promoters differentially regulated by nuclear factors related to craniofacial or neuronal development such as Sox9b, Sox10 and Runx2. We also predict that mef2cb gene may be post transcriptionally regulated by analysing the structure of its 5' UTR region, conserved throughout evolution. Our study provides new insights in MEF2C conservation and provides the first evidence of mef2cb regulation by both transcriptional and post transcriptional mechanisms, thus contributing to validate zebrafish as a good model for future studies concerning MEF2C dependent pathologies.

      PubDate: 2015-12-20T04:27:07Z
  • Mobilization of hyperacetylated mononucleosomes by purified yeast ISW2 in
    • Abstract: Publication date: Available online 12 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Wladyslaw A. Krajewski
      Catalytic activity of ISWI chromatin remodelers, which regulate nucleosome positioning on the DNA, depends on interactions of the putative acidic patch in ISWI helicase domain with the N-termini of nucleosomal H4 – such, that removal of H4 termini abolishes ISWI remodeling. Acetylation of H4 termini is also known to disrupt H4 interactions with acidic protein surfaces, and thus, histone acetylation could potentially impede ISWI functions. Since active chromatin in vivo is hyperacetylated, it is important to clarify if ISWI activities can function on the in vivo hyperacetylated nucleosomes. We evaluated if purified yeast ISW2 can act on mononucleosomes in which all four core histones are highly acetylated. Mononucleosomes were assembled using purified histones from mammalian CV1 cells grown in the presence of deacetylase inhibitor Trichostatin A (TSA). The CV1 cell line is characterized by fast kinetic of accumulation of highly acetylated histone isoforms in response to TSA treatment. However, such ‘native’ histone hyperacetylation had no apparent effects on the nucleosome remodeling propensities, suggesting that histone hyperacetylation does not necessarily block ISWI functions and that ISWI enzymes can function on active chromatin as well.

      PubDate: 2015-12-16T04:20:52Z
  • Testing the dependence of stabilizing effect of osmolytes on the
           fractional increase in the accessible surface area on thermal and chemical
           denaturations of proteins
    • Abstract: Publication date: Available online 12 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Safikur Rahman, Syed Ausaf Ali, Asimul Islam, Md. Imtaiyaz Hassan, Faizan Ahmad
      Here we have generated two different denatured states using heat- and guanidinium chloride (GdmCl) - induced denaturations of three disulfide bond free proteins (barstar, cytochrome-c and myoglobin). We have observed that these two denatured states of barstar and myoglobin are structurally and energetically different, for, heat-induced denatured state contains many un-melted residual structure that has a significant amount of secondary and tertiary interactions. We show that structural properties of the denatured state determine the magnitude of the protein stabilization in terms of Gibbs free energy change (ΔG D o) induced by an osmolyte, i.e., the greater the exposed surface area, the greater is the stabilization. Furthermore, we predicted the m-values (ability of osmolyte to fold or unfold proteins) using Tanford’s transfer-free energy model for the transfer of proteins to osmolyte solutions. We observed that, for each protein, m-value is comparable with our experimental data in cases of TMAO (trimethylamine-N-oxide) and sarcosine. However, a significant discrepancy between predicted and experimental m-values were observed in the case of glycine-betaine.

      PubDate: 2015-12-16T04:20:52Z
  • Alba from Thermoplasma volcanium belongs to α-NAT’s: An insight
           into the structural aspects of Tv Alba and its acetylation by Tv Ard1
    • Abstract: Publication date: Available online 30 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Chao Ma, Chinar Pathak, Sang Jae Lee, Ki-Young Lee, Sun-Bok Jang, Minjoo Nam, Hookang Im, Hye-Jin Yoon, Bong-Jin Lee
      The Alba superfamily proteins have been regarded as a conserved group of proteins in archaea and eukarya, which have shown to be important in nucleic acid binding, chromatic organization and gene regulation. These proteins often belong to the N-acetyltransferase (NAT) category (Nα-acetyltransferases or Nε-acetyltransferases) and undergo post-translational modifications. Here, we report the crystal structure of Alba from Thermoplasma volcanium (Tv Alba) at 2.4 Å resolution. The acetylation of Tv Alba was monitored and the N-terminal of Tv Alba has been shown to interact with acetyl coenzyme A (Ac-CoA). The chemical shift perturbation experiments of Tv Alba were performed in the presence of Ac-CoA and/or Tv Ard1, another T. volcanium protein that treats Tv Alba as a substrate. To examine the DNA binding capabilities of Tv Alba alone and in the presence of Ac-CoA and/or Tv Ard1, EMSA experiments were carried out. It is shown that although Tv Alba binds to Ac-CoA, the acetylation of Tv Alba is not related with its binding to dsDNA, and the involvement of the N-terminus in Ac-CoA binding demonstrates that Tv Alba belongs to the Nα-acetyltransferase family.

      PubDate: 2015-12-03T03:48:58Z
  • Fungal Cobalamin-independent methionine synthase: insights from the model
           organism, Neurospora crassa
    • Abstract: Publication date: Available online 30 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Robert W. Wheatley, Kenneth K.S. Ng, Manju Kapoor
      Two families of methionine synthases, distinct in catalytic and structural features, have been encountered: MetH, the cobalamin-dependent enzyme and MetE, the cobalamin-independent form. The MetE family is of mechanistic interest due to the chemically challenging nature of the reaction and is a potential target for antifungal therapeutics since the human genome encodes only MetH. Here we report the identification, purification, and crystal structure of MetE from the filamentous fungus Neurospora crassa (ncMetE). ncMetE was highly thermostable and crystalized readily, making it ideal for study. Crystal structures of native ncMetE in complex with either Zn2+or Cd2+ were solved at resolution limits of 2.10Å and 1.88Å, respectively. The monomeric protein contains two domains, each containing a (βα)8 barrel core, and a long α-helical segment spans the length of the protein, connecting the domains. Zn2+ bound in the C-terminal domain exhibits tetrahedral coordination with the side chains of His 652, Cys 654, Glu 676 and Cys 737. A Cd2+ replete structure revealed a supermetalated enzyme and demonstrated the inate flexibility of the metal binding site. An extensive analysis of sequence conservation within the MetE family identified 57 highly conserved residues and 60 additional residues that were conserved in all fungal sequences examined.

      PubDate: 2015-12-03T03:48:58Z
  • Intestinal mucosal changes and upregulated calcium transporter and FGF-23
    • Abstract: Publication date: Available online 30 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kannikar Wongdee, Jarinthorn Teerapornpuntakit, Chanakarn Sripong, Asma Longkunan, Wasutorn Chankamngoen, Chutiya Keadsai, Kamonshanok Kraidith, Nateetip Krishnamra, Narattaphol Charoenphandhu
      As the principal lactogenic hormone, prolactin (PRL) not only induces lactogenesis but also enhances intestinal calcium absorption to supply calcium for milk production. How the intestinal epithelium responses to PRL is poorly understood, but it is hypothesized to increase mucosal absorptive surface area and calcium transporter expression. Herein, lactating rats were found to have greater duodenal, jejunal and ileal villous heights as well as cecal crypt depths than age-matched nulliparous rats. Morphometric analyses in the duodenum and cecum showed that their mucosal adaptations were diminished by bromocriptine, an inhibitor of pituitary PRL release. PRL also upregulated calcium transporter expression (e.g., TRPV6 and PMCA1b) in the duodenum of lactating rats. Since excessive calcium absorption could be detrimental to lactating rats, local negative regulator of calcium absorption, e.g., fibroblast growth factor (FGF)-23, should be increased. Immunohistochemistry confirmed the upregulation of FGF-23 protein expression in the duodenal and cecal mucosae of lactating rats, consistent with the enhanced FGF-23 mRNA expression in Caco-2 cells. Bromocriptine abolished this lactation-induced FGF-23 expression. Additionally, FGF-23 could negate PRL-stimulated calcium transport across Caco-2 monolayer. In conclusion, PRL was responsible for the lactation-induced mucosal adaptations, which were associated with compensatory increase in FGF-23 expression probably to prevent calcium hyperabsorption.

      PubDate: 2015-12-03T03:48:58Z
  • Biochemistry and Regulation of the Protein Arginine Methyltransferases
    • Abstract: Publication date: Available online 2 December 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yalemi Morales, Tamar Cáceres, Kyle May, Joan M. Hevel
      Many key cellular processes can be regulated by the seemingly simple addition of one, or two, methyl groups to arginine residues by the nine known mammalian protein arginine methyltransferases (PRMTs). The impact that arginine methylation has on cellular well-being is highlighted by the ever growing evidence linking PRMT dysregulation to disease states, which has marked the PRMTs as prominent pharmacological targets. This review is meant to orient the reader with respect to the structural features of the PRMTs that account for catalytic activity, as well as provide a framework for understanding how these enzymes are regulated. An overview of what we understand about substrate recognition and binding is provided. Control of product specificity and enzyme processivity are introduced as necessary but flexible features of the PRMTs. Precise control of PRMT activity is a critical component to eukaryotic cell health, especially given that an arginine demethylase has not been identified. We therefore conclude the review with a comprehensive discussion of how protein arginine methylation is regulated.

      PubDate: 2015-12-03T03:48:58Z
  • Cellular toxicity of yeast prion protein Rnq1 can be modulated by
           N-terminal wild type huntingtin
    • Abstract: Publication date: Available online 26 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Ratnika Sethi, Vishal Patel, Aliabbas A. Saleh, Ipsita Roy
      Aggregation of the N-terminal human mutant huntingtin and the consequent toxicity in the yeast model of Huntington’s disease (HD) requires the presence of Rnq1 protein (Rnq1p) in its prion conformation [RNQ1+]. The understanding of interaction of wild-type huntingtin (wt-Htt) with the amyloidogenic prion has some gaps. In this work, we show that N-terminal fragment of wt-Htt (N-wt-Htt) ameliorated the toxic effect of [RNQ1+] depending on expression levels of both proteins. When the expression of N-wt-Htt was high, it increased the expression and delayed the aggregation of [RNQ1+]. As the expression of N-wt-Htt was reduced, it formed high molecular weight aggregates along with the prion. Even when sequestered by [RNQ1+], the beneficial effect of N-wt-Htt on expression of Rnq1p and on cell survival was evident. Huntingtin protein ameliorated toxicity due to the prion protein [RNQ1+] in yeast cells in a dose-dependent manner, resulting in increase in cell survival, hinting at its probable role as a component of the proteostasis network of the cell. Taking into account the earlier reports of the beneficial effect of expression of N-wt-Htt on the aggregation of mutant huntingtin, the function of wild-type huntingtin as an inhibitor of protein aggregation in the cell needs to be explored.

      PubDate: 2015-11-29T03:39:27Z
  • Structural changes upon peroxynitrite-mediated nitration of peroxiredoxin
           2; nitrated Prx2 resembles its disulfide-oxidized form
    • Abstract: Publication date: Available online 22 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Lía Randall, Bruno Manta, Kimberly J. Nelson, Javier Santos, Leslie B. Poole, Ana Denicola
      Peroxiredoxins are cys-based peroxidases that function in peroxide detoxification and H2O2-induced signaling. Human Prx2 is a typical 2-Cys Prx arranged as pentamers of head-to-tail homodimers. During the catalytic mechanism, the active-site cysteine (CP) cycles between reduced, sulfenic and disulfide state involving conformational as well as oligomeric changes. Several post-translational modifications were shown to affect Prx activity, in particular CP overoxidation which leads to inactivation. We have recently reported that nitration of Prx2, a post-translational modification on non-catalytic tyrosines, unexpectedly increases its peroxidase activity and resistance to overoxidation. To elucidate the cross-talk between this post-translational modification and the enzyme catalysis, we investigated the structural changes of Prx2 after nitration. Analytical ultracentrifugation, UV absorption, circular dicroism, steady-state and time-resolved fluorescence were used to connect catalytically relevant redox changes with tyrosine nitration. Our results show that the reduced nitrated Prx2 structurally resembles the disulfide-oxidized native form of the enzyme favoring a locally unfolded conformation that facilitates disulfide formation. These results provide structural basis for the kinetic analysis previously reported, the observed increase in activity and the resistance to overoxidation of the peroxynitrite-treated enzyme.

      PubDate: 2015-11-25T03:35:42Z
  • Interaction of the Serine Hydrolase KIAA1363 with Organophosphorus Agents:
           Evaluation of Potency and Kinetics
    • Abstract: Publication date: Available online 23 November 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Matthew K. Ross, Kim Pluta, Victoria Bittles, Abdolsamad Borazjani, J. Allen Crow
      Oxons are bioactive metabolites of organophosphorus insecticides (OPs) that covalently inactivate serine hydrolases. KIAA1363 is one of the most abundant serine hydrolases in mouse brain. Although the physiological consequences related to the inhibition of KIAA1363 due to environmental exposures to OPs are poorly understood, the enzyme was previously shown to have a role in the detoxification of oxons. Here, we overexpressed human KIAA1363 and CES1 in COS7 cells and compared the potency of inhibition (IC50s, 15 min) of KIAA1363 and CES1 by chlorpyrifos oxon (CPO), paraoxon (PO), and methyl paraoxon (MPO). The order of potency was CPO > PO >> MPO for both enzymes. We also determined the bimolecular rate constants (k inact/K i) for reactions of CPO and PO with KIAA1363 and CES1. KIAA1363 and CES1 were inactivated by CPO at comparable rates (4.4 x 106 s-1M-1 and 6.7 x 106 s-1M-1, respectively), whereas PO inactivated both enzymes at slower rates (0.4 x 106 s-1M-1 and 1.5 x 106 s-1M-1, respectively). Finally, the reactivation rate of KIAA1363 following inhibition by CPO was evaluated. Together, the results define the kinetics of inhibition of KIAA1363 by active metabolites of agrochemicals and indicate that KIAA1363 is highly sensitive to inhibition by these compounds.
      Graphical abstract image

      PubDate: 2015-11-25T03:35:42Z
  • 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
  • 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
  • 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
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