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  Subjects -> BIOLOGY (Total: 2629 journals)
    - BIOCHEMISTRY (198 journals)
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    - BIOLOGY (1326 journals)
    - BIOPHYSICS (43 journals)
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BIOCHEMISTRY (198 journals)                  1 2     

AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Chemical Biology     Full-text available via subscription   (Followers: 288)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 13)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 9)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 6)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 7)
Advances in Biological Chemistry     Open Access   (Followers: 5)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 6)
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: 10)
African Journal of Biochemistry Research     Open Access  
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: 6)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 169)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 11)
American Journal of Polymer Science     Open Access   (Followers: 17)
Amino Acids     Hybrid Journal   (Followers: 7)
Analytical Biochemistry     Hybrid Journal   (Followers: 193)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 28)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 10)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 18)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 7)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 4)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 9)
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)
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)
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 14)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 2)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 8)
Biochemical Genetics     Hybrid Journal   (Followers: 2)
Biochemical Journal     Full-text available via subscription   (Followers: 16)
Biochemical Pharmacology     Hybrid Journal   (Followers: 6)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 2)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 205)
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: 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: 4)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 3)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 18)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 6)
Biochimie     Hybrid Journal   (Followers: 4)
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 14)
BioDrugs     Full-text available via subscription   (Followers: 7)
Bioelectrochemistry     Hybrid Journal   (Followers: 3)
Biofuels     Hybrid Journal   (Followers: 7)
Biogeochemistry     Hybrid Journal   (Followers: 7)
BioInorganic Reaction Mechanisms     Full-text available via subscription   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 11)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Full-text available via subscription   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 6)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 17)
BMC Biochemistry     Open Access   (Followers: 8)
BMC Chemical Biology     Open Access   (Followers: 4)
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca : Food Science and Technology     Open Access  
Carbohydrate Polymers     Hybrid Journal   (Followers: 8)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 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: 5)
ChemBioChem     Hybrid Journal   (Followers: 2)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 23)
Chemical Engineering Journal     Hybrid Journal   (Followers: 19)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Full-text available via subscription   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 2)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 16)
Chemistry and Ecology     Hybrid Journal   (Followers: 1)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 3)
Clinical Chemistry and Laboratory Medicine     Full-text available via subscription   (Followers: 4)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 5)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 4)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 3)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 8)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 14)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 2)

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
   Journal TOC RSS feeds Export to Zotero [11 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
     Published by Elsevier Homepage  [2570 journals]   [SJR: 1.131]   [H-I: 115]
  • Multiple UDP- Glucuronosyltransferases in Human Liver Microsomes
           Glucuronidate Both R- and S-7-Hydroxywarfarin into Two Metabolites
    • Abstract: Publication date: Available online 19 October 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): C. Preston Pugh , Dakota L Pouncey , Jessica H. Hartman , Robert Nshimiyimana , Linda P. Desrochers , Thomas E. Goodwin , Gunnar Boysen , Grover P. Miller
      The widely used anticoagulant Coumadin (R/S-warfarin) undergoes oxidation by cytochromes P450 into hydroxywarfarins that subsequently become conjugated for excretion in urine. Hydroxywarfarins may modulate warfarin metabolism transcriptionally or through direct inhibition of cytochromes P450 and thus, UGT action toward hydroxywarfarin elimination may impact levels of the parent drugs and patient responses. Nevertheless, relatively little is known about conjugation by UDP-glucuronosyltransferases in warfarin metabolism. Herein, we identified probable conjugation sites, kinetic mechanisms and hepatic UGT isoforms involved in microsomal glucuronidation of R- and S-7-hydroxywarfarin. Both compounds underwent glucuronidation at C4 and C7 hydroxyl groups based on elution properties and spectral characteristics. Their formation demonstrated regio- and enantioselectivity by UGTs and resulted in either Michaelis-Menten or substrate inhibition kinetics. Glucuronidation at the C7 hydroxyl group occurred more readily than at the C4 group, and the reaction was overall more efficient for R-7-hydroxywarfarin due to higher affinity and rates of turnover. The use of these mechanisms and parameters to model in vivo clearance demonstrated that contributions of substrate inhibition would lead to underestimation of metabolic clearance than that predicted by Michaelis-Menten kinetics. Lastly, these processes were driven by multiple UGTs indicating redundancy in glucuronidation pathways and ultimately metabolic clearance of R- and S-7-hydroxywarfarin.
      Graphical abstract image

      PubDate: 2014-10-26T07:04:23Z
       
  • Cholesteryl ester diffusion, location and self-association constraints
           determine CETP activity with discoidal HDL: excimer probe study
    • Abstract: Publication date: Available online 22 October 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Alexander D. Dergunov , Elena V. Shabrova , Gennady E. Dobretsov
      The transfer of cholesteryl ester by recombinant cholesteryl ester transfer protein (CETP) between reconstituted discoidal high-density lipoprotein (rHDL) was studied. Particles contained apolipoprotein A-I, unsaturated POPC or saturated DPPC and cholesteryl ester as cholesteryl 1-pyrenedecanoate (CPD) or cholesteryl laurate (CL) in donor and acceptor rHDL, respectively. Probe dynamics fulfiled the quenching sphere-of-action model. The cholesteryl ester exchange between donor and acceptor particles was characterized by a heterogeneous kinetics; the fast exchanging CPD pool was much higher in a case of POPC compared to DPPC complexes. Probe fraction accessible to CETP increased with temperature, suggesting a more homogeneous probe distribution. Noncompetitive inhibition of probe transfer by acceptor particles was observed. The values of V max (0.063 μM·min-1) and catalytic rate constant k cat (0.42 s-1) together with a similarity of K m (0.9 μM CPD) and K I (2.8 μM CL) values for POPC-containing rHDL suggest the efficient cholesteryl ester transfer between nascent HDL with unsaturated phosphatidylcholine in vivo. The phospholipid matrix in discoidal HDL may underlie CETP activity through the self-association, diffusivity and location of cholesteryl ester in the bilayer, the accessibility of cholesteryl ester to cholesterol-binding site in apoA-I structure and the binding of cholesteryl ester, positionable by apoA-I, to CETP.


      PubDate: 2014-10-26T07:04:23Z
       
  • Characterization and identification of three novel aldo-keto reductases
           from Lodderomyces elongisporus for reducing ethyl 4-chloroacetoacetate
    • Abstract: Publication date: Available online 22 October 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Chenxi Ning , Erzheng Su , Dongzhi Wei
      Lodderomyces elongisporus LH703 isolated from soil samples contained three novel aldo-keto reductases (AKRs) (LEAKR 48, LEAKR 49, and LEAKR 50). The three enzymes were cloned, expressed, and purified to homogeneity for characterization. These three AKRs shared <40% amino acid identity with each other. LEAKR 50 was identified as a member of AKR3 family, whereas the other two LEAKRs were identified as members of two novel AKR families, respectively. All the three AKRs required nicotinamide adenine dinucleotide phosphate as a cofactor. However, they showed diverse characteristics, including optimum catalyzing conditions, resistance to adverse reaction conditions, and substrate specificity. LEAKR 50 was estimated to be a promising biocatalyst that could reduce ethyl 4-chloroacetoacetate with high enantiomeric excess (98% e. e.) and high activity residue under adverse conditions.


      PubDate: 2014-10-26T07:04:23Z
       
  • The contribution of activating transcription factor 3 to apoptosis of
           human colorectal cancer cells by protocatechualdehyde, a naturally
           occurring phenolic compound
    • Abstract: Publication date: Available online 22 October 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jeong Rak Lee , Man Hyo Lee , Hyun Ji Eo , Gwang Hun Park , Hun Min Song , Mi Kyoung Kim , Jin Wook Lee , Jin Boo Jeong
      Protocatechualdehyde (PCA) is one of the important compounds found in barley, green cavendish bananas and grapevine leaves. PCA shows anti-cancer activities in breast, leukemia and colorectal cancer cells. Previous study reported that PCA exerts anti-cancer activity through down-regulating cyclin D1 and HDAC2 in human colorectal cancer cells. However, the underlying mechanisms for the expression of activating transcription factor 3 (ATF3) by PCA has not been studied. Thus, we performed in vitro study to investigate if treatment of PCA affects ATF3 expression and ATF3-mediated apoptosis in human colorectal cancer cells. PCA decreased cell viability in a dose-dependent manner in HCT116 and SW480 cells. In addition, PCA reduced cell viability in MCF-7, MDA-MB-231 and HepG-2 cells. Exposure of PCA activated the levels of ATF3 protein and mRNA in HCT116 and SW480 cells. Inhibition of ERK1/2/ by PD98059 and p38 by SB203580 inhibited PCA-induced ATF3 expression and transcriptional activation. ATF3-knockdown inhibited PCA-induced apoptosis and cell viability. In addition, ATF3 overexpression enhanced PCA-mediated cleavage of PARP. These findings suggest that inhibition of cell viability and apoptosis by PCA may be result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.


      PubDate: 2014-10-26T07:04:23Z
       
  • The role of biotin and oxamate in the carboxyltransferase reaction of
           pyruvate carboxylase
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Adam D. Lietzan , Yi Lin , Martin St. Maurice
      Pyruvate carboxylase (PC) is a biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in central metabolism. During catalysis, carboxybiotin is translocated to the carboxyltransferase domain where the carboxyl group is transferred to the acceptor substrate, pyruvate. Many studies on the carboxyltransferase domain of PC have demonstrated an enhanced oxaloacetate decarboxylation activity in the presence of oxamate and it has been shown that oxamate accepts a carboxyl group from carboxybiotin during oxaloacetate decarboxylation. The X-ray crystal structure of the carboxyltransferase domain from Rhizobium etli PC reveals that oxamate is positioned in the active site in an identical manner to the substrate, pyruvate, and kinetic data are consistent with the oxamate-stimulated decarboxylation of oxaloacetate proceeding through a simple ping-pong bi bi mechanism in the absence of the biotin carboxylase domain. Additionally, analysis of truncated PC enzymes indicates that the BCCP domain devoid of biotin does not contribute directly to the enzymatic reaction and conclusively demonstrates a biotin-independent oxaloacetate decarboxylation activity in PC. These findings advance the description of catalysis in PC and can be extended to the study of related biotin-dependent enzymes.


      PubDate: 2014-10-12T04:08:23Z
       
  • Insulin inhibits AMPK activity and phosphorylates AMPK Ser485/491 through
           Akt in hepatocytes, myotubes and incubated rat skeletal muscle
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Rudy J. Valentine , Kimberly A. Coughlan , Neil B. Ruderman , Asish K. Saha
      Recent studies have highlighted the importance of an inhibitory phosphorylation site, Ser485/491, on the α-subunit of AMP-activated protein kinase (AMPK); however, little is known about the regulation of this site in liver and skeletal muscle. We examined whether the inhibitory effects of insulin on AMPK activity may be mediated through the phosphorylation of this inhibitory Ser485/491 site in hepatocytes, myotubes and incubated skeletal muscle. HepG2 and C2C12 cells were stimulated with or without insulin for 15-min. Similarly, rat extensor digitorum longus (EDL) muscles were treated +/− insulin for 10-min. Insulin significantly increased Ser485/491 p-AMPK under all conditions, resulting in a subsequent reduction in AMPK activity, ranging from 40% to 70%, despite no change in p-AMPK Thr172. Akt inhibition both attenuated the increase in Ser485/491 p-AMPK caused by insulin, and prevented the decrease in AMPK activity. Similarly, the growth factor IGF-1 stimulated Ser485/491 AMPK phosphorylation, and this too was blunted by inhibition of Akt. Inhibition of the mTOR pathway with rapamycin, however, had no effect on insulin-stimulated Ser485/491 p-AMPK. These data suggest that insulin and IGF-1 diminish AMPK activity in hepatocytes and muscle, most likely through Akt activation and the inhibitory phosphorylation of Ser485/491 on its α-subunit.


      PubDate: 2014-10-12T04:08:23Z
       
  • Conformational behaviour and aggregation of chickpea cystatin in
           trifluoroethanol: Effects of epicatechin and tannic acid
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Sheraz Ahmad Bhat , Bilqees Bano
      Conformational alterations and aggregates of chickpea cystatin (CPC) were investigated upon sequential addition of trifluoroethanol (TFE) over a range of 0–70% v/v. CPC on 30% and 40% v/v TFE addition exhibited non-native β-sheet, altered intrinsic fluorescence, increased thioflavin T fluorescence, prominent red shifted shoulder peak in Congo red absorbance, and enhanced turbidity as well as Rayleigh scattering, suggesting the aggregate formation. TEM results confirmed the formation of fibrillar aggregates at 30% and 40% v/v TFE. On increasing concentration of TFE to 70% v/v, CPC showed retention of native-like secondary structure, increased intrinsic and ANS fluorescence. Thus our results show that favourable condition for fibrillation of CPC is in the range of 30–40% TFE. Moreover, anti-aggregational effects of polyphenols, epicatechin (EC) and tannic acid (TA) were analysed using ThT binding assay and other biophysical assays. EC and TA produced a concentration dependent decline in ThT fluorescence suggesting inhibition of the fibril formation. Furthermore, TA in comparison to EC, served as a more effective inhibitor against amyloid fibril formation of CPC. This work supports the universality of the amyloid-like aggregation not restricted to some special categories of protein and the fact that this aggregation can be prevented.


      PubDate: 2014-10-12T04:08:23Z
       
  • A computational study of the dechlorination of
           β-hexachlorocyclohexane (β-HCH) catalyzed by the haloalkane
           dehalogenase LinB
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Rabindra Nath Manna , Agnieszka Dybala-Defratyka
      LinB, a haloalkane dehalogenase from Sphingomonas paucimobilis UT26, is known to metabolize halohydrocarbons to halide ions and the respective alcohols. Its broad substrate specificity allowed its consideration for bioremediation. Herein, we have shown its catalytic action toward β-hexachlorocyclohexane (β-HCH) – an example of large-size substrates that can be accommodated in its active site. We have analyzed the capability of combined QM/MM schemes to describe in detail the SN2 dechlorination reaction between β-HCH and Asp108 in the active site of LinB. Free energy surfaces have been calculated using one and two dimensional potentials of mean force (PMF) obtained at the PM3/MM (MM=amberff99SB, TIP3P) level of theory. The overestimated energetic barriers by the PM3 Hamiltonian were corrected using a DFT functional (M06-2X). The resulted activation energies (16 and 19kcalmol−1 from 1D and 2D-PMF profiles, respectively) for the dechlorination reaction of β-HCH in the active site of LinB enzyme are in qualitative agreement with the experimentally determined value of 17kcalmol−1. The binding of β-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger δ-hexabromocyclododecane (δ-HBCD).
      Graphical abstract image

      PubDate: 2014-10-12T04:08:23Z
       
  • Role of calpain-1 in the early phase of experimental ALS
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): R. Stifanese , M. Averna , R. De Tullio , M. Pedrazzi , M. Milanese , T. Bonifacino , G. Bonanno , F. Salamino , S. Pontremoli , E. Melloni
      Elevation in [Ca2+] i and activation of calpain-1 occur in central nervous system of SOD1G93A transgenic mice model of amyotrophic lateral sclerosis (ALS), but few data are available about the early stage of ALS. We here investigated the level of activation of the Ca2+-dependent protease calpain-1 in spinal cord of SOD1G93A mice to ascertain a possible role of the protease in the aetiology of ALS. Comparing the events occurring in the 120day old mice, we found that [Ca2+] i and activation of calpain-1 were also increased in the spinal cord of 30day old mice, as indicated by the digestion of some substrates of the protease such as nNOS, αII-spectrin, and the NR2B subunit of NMDA-R. However, the digestion pattern of these proteins suggests that calpain-1 may play different roles depending on the phase of ALS. In fact, in spinal cord of 30day old mice, activation of calpain-1 produces high amounts of nNOS active species, while in 120day old mice enhanced-prolonged activation of calpain-1 inactivates nNOS and down-regulates NR2B. Our data reveal a critical role of calpain-1 in the early phase and during progression of ALS, suggesting new therapeutic approaches to counteract its onset and fatal course.


      PubDate: 2014-10-12T04:08:23Z
       
  • Differential phosphorylation of LZ+/LZ− MYPT1 isoforms regulates MLC
           phosphatase activity
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Samantha L. Yuen , Ozgur Ogut , Frank V. Brozovich
      The vascular response to NO is due, in part, to a Ca2+ independent activation of myosin light chain (MLC) phosphatase, a trimeric enzyme of 20kDa, 38kDa catalytic and 110–130kDa myosin targeting (MYPT1) subunits. Alternative mRNA splicing produces MYPT1 isoforms that differ by the presence or absence of a central insert (CI) and a leucine zipper (LZ), and the presence of a LZ+ MYPT1 isoform is important for protein kinase G (PKG) mediated activation of MLC phosphatase. This study was designed to determine the molecular basis for the differential sensitivity of the vasculature to NO. Our results demonstrate that the presence of the MYPT1 LZ domain is required for PKG to both phosphorylate MYPT1 at S668 and activate MLC phosphatase. Further for LZ+ MYPT1 isoforms, an S668A MYPT1 mutation prevents the PKG mediated, Ca2+ independent activation of MLC phosphatase. These data demonstrate that differential PKG mediated S668 phosphorylation of LZ+/LZ− MYPT1 isoforms could be important for determining the diversity in the sensitivity of the vasculature to NO mediated vasodilatation. Thus, the relative expression of LZ+/LZ− MYPT1 isoforms, in part, defines the vascular response to NO and NO based vasodilators, and therefore, plays a role in the regulation of vascular tone in both health and disease.


      PubDate: 2014-10-12T04:08:23Z
       
  • Hypoxic conditions differentially regulate TAZ and YAP in cancer cells
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Libo Yan , Qingchun Cai , Yan Xu
      The Hippo-YAP pathway is altered and implicated as an oncogenic signaling pathway in many human cancers. Hypoxia is an important microenvironmental factor that promotes tumorigenesis. However, the effects of hypoxia on the two most important Hippo-YAP effectors, YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif), have not been reported. In this work, we demonstrated that TAZ was functionally involved in cell proliferation and/or migration in epithelial ovarian cancer (EOC) or human ovarian surface epithelial (HOSE) cells. Hypoxic conditions (1% O2 or hypoxia mimics) induced a reduction of YAP phosphorylation (S127) and total YAP expression in EOC cell lines OVCAR5 and SKOV3. However, these conditions up-regulated levels of S69 phosphorylated TAZ in EOC cells. The known TAZ kinases, Lats1 and Akt, were unlikely to be involved in up-regulated pTAZ by hypoxic conditions. Together, our data revealed new and differential regulating mechanisms of TAZ and YAP in cancer cells by hypoxia conditions.


      PubDate: 2014-10-12T04:08:23Z
       
  • Tumor suppressor gene ING3 induces cardiomyocyte hypertrophy via
           inhibition of AMPK and activation of p38 MAPK signaling
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Jiaojiao Wang , Zhiping Liu , Xiaojun Feng , Si Gao , Suowen Xu , Peiqing Liu
      Cardiac hypertrophy, an adaptive growth process that occurs in response to various pathophysiological stimuli, constitutes an important risk factor for the development of heart failure. However, the molecular mechanisms that regulate this cardiac growth response are not completely understood. Here we revealed that ING3 (inhibitor of growth family, member 3), a type II tumor suppressor, plays a critical role in the regulation of cardiac hypertrophy. ING3 expression was present in relatively high abundance in the heart, and was prominently upregulated in hypertrophic agonists angiotensin II (Ang II), phenylephrine (PE), or isoproterenol (ISO)-stimulated cardiomyocytes and in hearts of rat undergoing abdominal aortic constriction (AAC) surgery. In cardiomyocytes, overexpression of ING3 caused an increase in ANP, BNP and β-MHC mRNA levels and cell surface area, while depletion of ING3 attenuated PE-induced cardiomyocyte hypertrophy. Mechanistically, we have demonstrated that overexpression of ING3 could inactivate the AMPK and activate the canonical p38 MAPK signaling. Remarkably, AMPK agonist AICAR or p38 MAPK inhibitor SB203580 abrogated ING3-induced hypertrophic response in cardiomyocytes. In summary, our data disclose a novel role of ING3 as an inducer of pathological cardiac hypertrophy, suggesting that silencing of ING3 may be explored as a potential therapeutic target in preventing cardiac hypertrophy.


      PubDate: 2014-10-12T04:08:23Z
       
  • Diversity of reaction characteristics of glucan branching enzymes and the
           fine structure of α-glucan from various sources
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Takayuki Sawada , Yasunori Nakamura , Takashi Ohdan , Asami Saitoh , Perigio B. Francisco Jr. , Eiji Suzuki , Naoko Fujita , Takahiro Shimonaga , Shoko Fujiwara , Mikio Tsuzuki , Christophe Colleoni , Steven Ball
      To investigate the functional properties of 10 α-glucan branching enzymes (BEs) from various sources, we determined the chain-length distribution of BE enzymatic products and their phosphorylase-limit dextrins (Φ-LD). All BEs could be classified into either of the three rice BE isozymes: OsBEI, OsBEIIa, or OsBEIIb. Escherichia coli BE (EcoBE) had the same enzymatic properties as OsBEI, while Synechococcus elongatus BE (ScoBE) and Chlorella kessleri BE (ChlBE) had BEIIb-type properties. Human BE (HosBE), yeast BE (SacBE), and two Porphyridium purpureum BEs (PopBE1 and PopBE2) exhibited the OsBEIIa-type properties. Analysis of chain-length profile of Φ-LD of the BE reaction products revealed that EcoBE, ScoBE, PopBE1, and PopBE2 preferred A-chains as acceptors, while OsBEIIb used B-chains more frequently than A-chains. Both EcoBE and ScoBE specifically formed the branch linkages at the third glucose residue from the reducing end of the acceptor chain. The present results provide evidence for the first time that great variation exists as to the preference of BEs for their acceptor chain, either A-chain or B-chain. In addition, EcoBE and ScoBE recognize the location of branching points in their acceptor chain during their branching reaction. Nevertheless, no correlation exists between the primary structure of BE proteins and their enzymatic characteristics.


      PubDate: 2014-10-12T04:08:23Z
       
  • Mechanisms and targets of the modulatory action of S-nitrosoglutathione
           (GSNO) on inflammatory cytokines expression
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Alessandro Corti , Maria Franzini , Ilenia Scataglini , Alfonso Pompella
      A number of experimental studies has documented that S-nitrosoglutathione (GSNO), the main endogenous low-molecular-weight S-nitrosothiol, can exert modulatory effects on inflammatory processes, thus supporting its potential employment in medicine for the treatment of important disease conditions. At molecular level, GSNO effects have been shown to modulate the activity of a series of transcription factors (notably NF-κB, AP-1, CREB and others) as well as other components of signal transduction chains (e.g. IKK-β, caspase 1, calpain and others), resulting in the modulation of several cytokines and chemokines expression (TNFα, IL-1β, IFN-γ, IL-4, IL-8, RANTES, MCP-1 and others). Results reported to date are however not univocal, and a single main mechanism of action for the observed anti-inflammatory effects of GSNO has not been identified. Conflicting observations can be explained by differences among the various cell types studies as to the relative abundance of enzymes in charge of GSNO metabolism (GSNO reductase, γ-glutamyltransferase, protein disulfide isomerase and others), as well as by variables associated with the individual experimental models employed. Altogether, anti-inflammatory properties of GSNO seem however to prevail, and exploration of the therapeutic potential of GSNO and analogues appears therefore warranted.
      Graphical abstract image

      PubDate: 2014-10-12T04:08:23Z
       
  • Mechanism of 2′,3′-dimethoxyflavanone-induced apoptosis in
           breast cancer stem cells: Role of ubiquitination of caspase-8 and LC3
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Thao Anh Tran , Kwang Seok Ahn , Yeon Woo Song , Jeong Yong Moon , Moonjae Cho , Yoongho Lim , Somi Kim Cho
      Accumulating evidence has displayed that targeting cancer stem cells (CSCs) is a very promising way for anti-cancer therapies. 2′,3′-Dimethoxyflavanone (2′,3′-DMF) showed the most potent toxicity of a group of 42 flavonoids tested in MCF-7-SC breast cancer stem cells. 2′,3′-DMF triggered intrinsic and extrinsic apoptosis by stimulating the cleavage of PARP and the activation of caspase-9, -8, and -3. Interestingly, 2′,3′-DMF induces a dramatic increase in the conversion of LC3, a well-known marker for autophagy. However, acidic vesicular organelles (AVOs), one of the autophagic flux markers were not detected. Co-treatment with chloroquine, the lysosomal inhibitor that blocks autophagic degradation did not show any change in the degree of LC3 conversion, implying that LC3 could play a role in the non-autophagic cell death of MCF-7-SC. We found that 2′,3′-DMF induces the ubiquitination of caspase-8, this resulted in an interaction between caspase-8 and LC3, which led to the aggregation and activation of caspase-8. Co-treating cells with 2′,3′-DMF and 3-methyladenine, an inhibitor of LC3 lipidation, reduced the activation of caspase-8. These findings provide novel insights into the anti-cancer effects of 2′,3′-DMF in breast cancer stem cells by revealing that it induced apoptosis in accompany with the activation of caspase-8 mediated by LC3 conversion.


      PubDate: 2014-10-12T04:08:23Z
       
  • The metastability of human UDP-galactose 4′-epimerase (GALE) is
           increased by variants associated with type III galactosemia but decreased
           by substrate and cofactor binding
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Angel L. Pey , Esperanza Padín-Gonzalez , Noel Mesa-Torres , David J. Timson
      Type III galactosemia is an inherited disease caused by mutations which affect the activity of UDP-galactose 4′-epimerase (GALE). We evaluated the impact of four disease-associated variants (p.N34S, p.G90E, p.V94M and p.K161N) on the conformational stability and dynamics of GALE. Thermal denaturation studies showed that wild-type GALE denatures at temperatures close to physiological, and disease-associated mutations often reduce GALE’s thermal stability. This denaturation is under kinetic control and results partly from dimer dissociation. The natural ligands, NAD+ and UDP-glucose, stabilize GALE. Proteolysis studies showed that the natural ligands and disease-associated variations affect local dynamics in the N-terminal region of GALE. Proteolysis kinetics followed a two-step irreversible model in which the intact protein is cleaved at Ala38 forming a long-lived intermediate in the first step. NAD+ reduces the rate of the first step, increasing the amount of undigested protein whereas UDP-glucose reduces the rate of the second step, increasing accumulation of the intermediate. Disease-associated variants affect these rates and the amounts of protein in each state. Our results also suggest communication between domains in GALE. We hypothesize that, in vivo, concentrations of natural ligands modulate GALE stability and that it should be possible to discover compounds which mimic the stabilising effects of the natural ligands overcoming mutation-induced destabilization.
      Graphical abstract image

      PubDate: 2014-10-12T04:08:23Z
       
  • Electrophysiological characterization of human Na+/taurocholate
           cotransporting polypeptide (hNTCP) heterologously expressed in Xenopus
           laevis oocytes
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Masayuki Masuda , Yukari Ichikawa , Kazumi Shimono , Maki Shimizu , Yoshio Tanaka , Toshifumi Nara , Seiji Miyauchi
      The Na+/taurocholate cotransporting polypeptide (NTCP) plays a major role in Na+-dependent bile acid uptake into hepatocytes. The purpose of the present study was to establish the heterologous expression of human NTCP (hNTCP) in Xenopus laevis oocytes and to elucidate whether the transport of bile acid via hNTCP is electrogenic using electrophysiological techniques. First, we evaluated the uptake of taurocholate (TCA) by hNTCP heterologously expressed in Xenopus oocytes utilizing [3H]-labeled TCA. The uptake of 1.2μM TCA by cRNA-injected oocytes increased more than 100-fold compared to H2O-injected oocytes, indicating that hNTCP is robustly expressed in the oocytes. hNTCP-mediated transport of TCA is saturable with a Michaelis constant of 10.5±2.9μM. The Na+-activation kinetics describing the relationship between the concentration of Na+ and the magnitude of the TCA uptake rate by hNTCP were sigmoidal with a Hill coefficient of 2.3±0.4, indicating the involvement of more than one Na+ in the transport process. Ntcp in primary cultured hepatocytes from rats exhibited similar Na+-activation kinetics of TCA uptake rate with a Hill coefficient of 1.9±0.1, suggesting that hNTCP could be expressed properly in the oocytes and exhibit the electrogenic property of Na+-coupled TCA transport. The transport of TCA via hNTCP was subsequently determined in the oocytes by the inward currents induced via TCA uptake under voltage (−50mV). Two hundred micromolar TCA induced significant inward currents that were entirely abolished by the substitution of Na+ with N-methyl-d-glucamine (NMDG) in the perfusate, indicating that the TCA-induced currents were obligatorily dependent on the presence of Na+. The TCA-induced currents were saturable, and the substrate concentration needed for half-maximal induction of the current was consistent with the Michaelis constant. Transportable substrates, such as rosuvastatin and fluvastatin, also induced currents. These results in the hNTCP heterologously expressed in Xenopus oocytes directly demonstrated that hNTCP is an electrogenic Na+-dependent transporter.


      PubDate: 2014-10-12T04:08:23Z
       
  • Corrigendum to “Having excess levels of PCSK9 is not sufficient to
           induce complex formation between PCSK9 and the LDL receptor” [Arch
           Biochem Biophys 545 (2014) 124–132]
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Catherine J. Wooten , Audrey F. Adcock , DaTonye I. Agina-Obu , Dayami Lopez



      PubDate: 2014-10-12T04:08:23Z
       
  • Corrigendum to “Phytoestrogen consumption and association with
           breast, prostate and colorectal cancer in EPIC Norfolk” [Arch
           Biochem Biophys 501 (2010) 170–175]
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Heather A. Ward , Gunter G.C. Kuhnle



      PubDate: 2014-10-12T04:08:23Z
       
  • Corrigendum to “Identification, characterization, and crystal
           structure of an aldo–keto reductase (AKR2E4) from the silkworm
           Bombyx mori” [Arch Biochem Biophys 538 (2013) 156–163]
    • Abstract: Publication date: 15 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 562
      Author(s): Kohji Yamamoto , David K. Wilson



      PubDate: 2014-10-12T04:08:23Z
       
  • Bone, a dynamic and integrating tissue
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Bram C.J. van der Eerden , Anna Teti , Willian F. Zambuzzi



      PubDate: 2014-10-12T04:08:23Z
       
  • Osteoblast and osteocyte: Games without frontiers
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Mattia Capulli , Riccardo Paone , Nadia Rucci
      The portrait of osteoblasts and osteocytes has been subjected to a revision, since a large body of evidence is attributing these cells amazing roles both inside and outside the bone. The osteoblast, long confined to its bone building function, is actually a very eclectic cell, actively regulating osteoclast formation and function as well as hematopoietic stem cells homeostasis. It is also an endocrine cell, affecting energy metabolism, male fertility and cognition through the release of osteocalcin, a perfect definition-fitting hormone in its uncarboxylated state. As for the osteocytes, many evidence shows that they do not merely represent the final destination of the osteoblasts, but they are instead very active cells that, besides a mechanosensorial function, actively contribute to the bone remodelling by regulating bone formation and resorption. The regulation is exerted by the production of sclerostin (SOST), which in turn inhibits osteoblast differentiation by blocking Wnt/beta-catenin pathway. At the same time, osteocytes influence bone resorption both indirectly, by producing RANKL, which stimulates osteoclastogenesis, and directly by means of a local osteolysis, which is observed especially under pathological conditions. The great versatility of both these cells reflects the complexity of the bone tissue, which has not only a structural role, but influences and is influenced by different organs, taking part in homeostatic and adaptive responses affecting the whole organism.


      PubDate: 2014-10-12T04:08:23Z
       
  • Reprint of: The Great Beauty of the osteoclast
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Alfredo Cappariello , Antonio Maurizi , Vimal Veeriah , Anna Teti
      Much has been written recently on osteoclast biology, but this cell type still astonishes scientists with its multifaceted functions and unique properties. The last three decades have seen a change in thinking about the osteoclast, from a cell with a single function, which just destroys the tissue it belongs to, to an “orchestrator” implicated in the concerted regulation of bone turnover. Osteoclasts have unique morphological features, organelle distribution and plasma membrane domain organization. They require polarization to cause extracellular bone breakdown and release of the digested bone matrix products into the circulation. Osteoclasts contribute to the control of skeletal growth and renewal. Alongside other organs, including kidney, gut, thyroid and parathyroid glands, they also affect calcemia and phosphatemia. Osteoclasts are very sensitive to pro-inflammatory stimuli, and studies in the ‘00s ascertained their tight link with the immune system, bringing about the question why bone needs a cell regulated by the immune system to remove the extracellular matrix components. Recently, osteoclasts have been demonstrated to contribute to the hematopoietic stem cell niche, controlling local calcium concentration and regulating the turnover of factors essential for hematopoietic stem cell mobilization. Finally, osteoclasts are important regulators of osteoblast activity and angiogenesis, both by releasing factors stored in the bone matrix, and secreting “clastokines” that regulate the activity of neighboring cells. All these facets will be discussed in this review article, with the aim of underscoring The Great Beauty of the osteoclast.


      PubDate: 2014-10-12T04:08:23Z
       
  • Regulation of cortical and trabecular bone mass by communication between
           osteoblasts, osteocytes and osteoclasts
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Natalie A. Sims , Christina Vrahnas
      The size and strength of bone is determined by two fundamental processes. One process, bone remodelling, renews the skeleton throughout life. In this process existing bone is resorbed by osteoclasts and replaced, in the same location, by osteoblasts. The other process is bone modelling, where bone formation and resorption occur at different sites so that the shape of bone is changed. Recent data suggests that both remodelling and modelling are controlled by signals between the cells that carry out these two processes. Osteoclasts both resorb bone, and provide inhibitory and stimulatory signals, including cardiotrophin-1 and sphingosine-1-kinase, to the osteoblast lineage thereby regulating their differentiation and activity on both trabecular and cortical surfaces. In addition, the osteoblast lineage, including osteoblast progenitors, matrix-producing osteoblasts, bone lining cells, and matrix-embedded osteocytes, produce both inhibitory and stimulatory factors that stimulate osteoclast differentiation. We will discuss the roles of osteoblast- and osteocyte-derived RANKL, and paracrine, autocrine and endocrine factors, such as ephrinB2, the IL-6/gp130 family of cytokines, parathyroid hormone, and its related peptide, PTHrP. These factors not only stimulate RANKL production, but also stimulate osteoblast differentiation and activity. This review will focus on recent data, generated from pharmacological and genetic studies of mouse models and what these data reveal about these pathways at different stages of osteoblast differentiation and their impact on both bone remodelling and modelling in trabecular and cortical bone.


      PubDate: 2014-10-12T04:08:23Z
       
  • Roles of osteoclasts in the control of medullary hematopoietic niches
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Claudine Blin-Wakkach , Matthieu Rouleau , Abdelilah Wakkach
      Bone marrow is the major site of hematopoiesis in mammals. The bone marrow environment plays an essential role in the regulation of hematopoietic stem and progenitor cells by providing specialized niches in which these cells are maintained. Many cell types participate to the composition and regulation of hematopoietic stem cell (HSC) niches, integrating complex signals from the bone, immune and nervous systems. Among these cells, the bone-resorbing osteoclasts (OCLs) have been described as main regulators of HSC niches. They are not limited to carving space for HSCs, but they also provide signals that affect the molecular and cellular niche components. However, their exact role in HSC niches remains unclear because of the variety of models, signals and conditions used to address the question. The present review will discuss the importance of the implication of OCLs focusing on the formation of HSC niches, the maintenance of HSCs in these niches and the mobilization of HSCs from the bone marrow. It will underline the importance of OCLs in HSC niches.


      PubDate: 2014-10-12T04:08:23Z
       
  • Extracellular vesicles: Specialized bone messengers
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Jess Morhayim , Marta Baroncelli , Johannes P. van Leeuwen
      Mammalian cells actively secrete factors that contribute to shape their microenvironment. These factors either travel freely or they are enclosed within the lipid bilayer of extracellular vesicles (EVs), and regulate the function of neighboring and distant cells. EVs are secreted by a wide spectrum of cell types and are found in various biological fluids. They convey their message by mediating the horizontal transfer of bioactive molecules, such as proteins, mRNAs and miRNAs, between cells. Recent studies showed the vital roles of EVs in a wide range of physiological and pathophysiological processes. In this review, we highlight the recent developments in the newly emerging EV field, including their biogenesis, molecular content and function. Moreover, we discuss the role of EVs in bone biology and their promising applications in diagnosis, drug development and regenerative therapy.


      PubDate: 2014-10-12T04:08:23Z
       
  • MicroRNAs in the skeleton: Cell-restricted or potent intercellular
           communicators'
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Bram C.J. van der Eerden
      MicroRNAs (miRNAs) play a fundamental role in cell proliferation, differentiation and apoptosis and have been associated with many diseases and physiological states. Within the skeleton, both the bone forming cells, osteoblasts, and the bone degrading cells, osteoclasts, are mostly being stimulated by miRNAs through downregulation of inhibitors of bone cell differentiation. Besides miRNAs affecting master genes of bone cell differentiation and function in a cell-restricted manner, evidence is gathering that miRNAs are excreted into the local environment but also into the circulation, implicating a role for miRNAs in nearby or even distant target cells. In this review, the most recent novel miRNAs implicated in bone cell differentiation regulation will be described but also their potential paracrine or endocrine role, thus reinforcing the concept that miRNAs may function as powerful communicators between cell types or tissues.


      PubDate: 2014-10-12T04:08:23Z
       
  • Matrix Gla protein and osteocalcin: From gene duplication to
           neofunctionalization
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): M. Leonor Cancela , Vincent Laizé , Natércia Conceição
      Osteocalcin (OC or bone Gla protein, BGP) and matrix Gla protein (MGP) are two members of the growing family of vitamin K-dependent (VKD) proteins. They were the first VKD proteins found not to be involved in coagulation and synthesized outside the liver. Both proteins were isolated from bone although it is now known that only OC is synthesized by bone cells under normal physiological conditions, but since both proteins can bind calcium and hydroxyapatite, they can also accumulate in bone. Both OC and MGP share similar structural features, both in terms of protein domains and gene organization. OC gene is likely to have appeared from MGP through a tandem gene duplication that occurred concomitantly with the appearance of the bony vertebrates. Despite their relatively close relationship and the fact that both can bind calcium and affect mineralization, their functions are not redundant and they also have other unrelated functions. Interestingly, these two proteins appear to have followed quite different evolutionary strategies in order to acquire novel functionalities, with OC following a gene duplication strategy while MGP variability was obtained mostly by the use of multiple promoters and alternative splicing, leading to proteins with additional functional characteristics and alternative gene regulatory pathways.


      PubDate: 2014-10-12T04:08:23Z
       
  • Bone Morphogenetic Proteins: Structure, biological function and
           therapeutic applications
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Ana Claudia Carreira , Gutemberg Gomes Alves , William Fernando Zambuzzi , Mari Cleide Sogayar , José Mauro Granjeiro
      Bone Morphogenetic Proteins (BMPs) are multifunctional secreted cytokines, which belong to the TGF-β superfamily. These glycoproteins act as a disulfide-linked homo- or heterodimers, being potent regulators of bone and cartilage formation and repair, cell proliferation during embryonic development and bone homeostasis in the adult. BMPs are promising molecules for tissue engineering and bone therapy. The present review discusses this family of proteins, their structure and biological function, their therapeutic applications and drawbacks, their effects on mesenchymal stem cells differentiation, and the cell signaling pathways involved in this process.


      PubDate: 2014-10-12T04:08:23Z
       
  • Bone tissue remodeling and development: Focus on matrix metalloproteinase
           functions
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Katiucia Batista Silva Paiva , José Mauro Granjeiro
      Bone-forming cells originate from distinct embryological layers, mesoderm (axial and appendicular bones) and ectoderm (precursor of neural crest cells, which mainly form facial bones). These cells will develop bones by two principal mechanisms: intramembranous and endochondral ossification. In both cases, condensation of multipotent mesenchymal cells occurs, at the site of the future bone, which differentiate into bone and cartilage-forming cells. During long bone development, an initial cartilaginous template is formed and replaced by bone in a coordinated and refined program involving chondrocyte proliferation and maturation, vascular invasion, recruitment of adult stem cells and intense remodeling of cartilage and bone matrix. Matrix metalloproteinases (MMPs) are the most important enzymes for cleaving structural components of the extracellular matrix (ECM), as well as other non-ECM molecules in the ECM space, pericellular perimeter and intracellularly. Thus, the bioactive molecules generated act on several biological events, such as development, tissue remodeling and homeostasis. Since the discovery of collagenase in bone cells, more than half of the MMP members have been detected in bone tissues under both physiological and pathological conditions. Pivotal functions of MMPs during development and bone regeneration have been revealed by knockout mouse models, such as chondrocyte proliferation and differentiation, osteoclast recruitment and function, bone modeling, coupling of bone resorption and formation (bone remodeling), osteoblast recruitment and survival, angiogenesis, osteocyte viability and function (biomechanical properties); as such alterations in MMP function may alter bone quality. In this review, we look at the principal properties of MMPs and their inhibitors (TIMPs and RECK), provide an up-date on their known functions in bone development and remodeling and discuss their potential application to Bone Bioengineering.


      PubDate: 2014-10-12T04:08:23Z
       
  • Cellular behavior as a dynamic field for exploring bone bioengineering: A
           closer look at cell–biomaterial interface
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Sara Gemini-Piperni , Esther Rieko Takamori , Suelen Cristina Sartoretto , Katiúcia B.S. Paiva , José Mauro Granjeiro , Rodrigo Cardoso de Oliveira , Willian Fernando Zambuzzi
      Bone is a highly dynamic and specialized tissue, capable of regenerating itself spontaneously when afflicted by minor injuries. Nevertheless, when major lesions occur, it becomes necessary to use biomaterials, which are not only able to endure the cellular proliferation and migration, but also to substitute the original tissue or integrate itself to it. With the life expectancy growth, regenerative medicine has been gaining constant attention in the reconstructive field of dentistry and orthopedy. Focusing on broadening the therapeutic possibilities for the regeneration of injured organs, the development of biomaterials allied with the applicability of gene therapy and bone bioengineering has been receiving vast attention over the recent years. The progress of cellular and molecular biology techniques gave way to new-guided therapy possibilities. Supported by multidisciplinary activities, tissue engineering combines the interaction of physicists, chemists, biologists, engineers, biotechnologist, dentists and physicians with common goals: the search for materials that could promote and lead cell activity. A well-oriented combining of scaffolds, promoting factors, cells, together with gene therapy advances may open new avenues to bone healing in the near future. In this review, our target was to write a report bringing overall concepts on tissue bioengineering, with a special attention to decisive biological parameters for the development of biomaterials, as well as to discuss known intracellular signal transduction as a new manner to be explored within this field, aiming to predict in vitro the quality of the host cell/material and thus contributing with the development of regenerative medicine.


      PubDate: 2014-10-12T04:08:23Z
       
  • Osseointegration of metallic devices: Current trends based on implant
           hardware design
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Paulo G. Coelho , Ryo Jimbo
      Osseointegration of metallic devices has been one of the most successful treatments in rehabilitative dentistry and medicine over the past five decades. While highly successful, the quest for designing surgical instrumentation and associated implantable devices that hastens osseointegration has been perpetual and has often been approached as single variable preclinical investigations. The present manuscript presents how the interplay between surgical instrumentation and device macrogeometry not only plays a key role on both early and delayed stages of osseointegration, but may also be key in how efficient smaller length scale designing (at the micrometer and nanometer scale levels) may be in hastening early stages of osseointegration.


      PubDate: 2014-10-12T04:08:23Z
       
  • Role of angiogenesis in bone repair
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Uttara Saran , Sara Gemini Piperni , Suvro Chatterjee
      Bone vasculature plays a vital role in bone development, remodeling and homeostasis. New blood vessel formation is crucial during both primary bone development as well as fracture repair in adults. Both bone repair and bone remodeling involve the activation and complex interaction between angiogenic and osteogenic pathways. Interestingly studies have demonstrated that angiogenesis precedes the onset of osteogenesis. Indeed reduced or inadequate blood flow has been linked to impaired fracture healing and old age related low bone mass disorders such as osteoporosis. Similarly the slow penetration of host blood vessels in large engineered bone tissue grafts has been cited as one of the major hurdle still impeding current bone construction engineering strategies. This article reviews the current knowledge elaborating the importance of vascularization during bone healing and remodeling, and the current therapeutic strategies being adapted to promote and improve angiogenesis.


      PubDate: 2014-10-12T04:08:23Z
       
  • The immune system, bone and RANKL
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Matteo M. Guerrini , Hiroshi Takayanagi
      Bone and immune systems are tightly linked. In the past years, many molecules originally believed to belong to the immune system were found to function in bone cells. It is now evident that the two systems are coregulated by many shared cytokines and signaling molecules. Here we exemplify the complex interaction between bone metabolism and immune response focusing on the multifaceted role of receptor activator of NF-κB ligand (RANKL). RANKL is expressed by cells of both systems, is an essential regulator of bone degradation and exerts either pro or anti-inflammatory effects on the immune response. In the present review, we summarize the multiple functions of RANKL in bone and in the immune systems, aiming to provide an overview of the field of osteoimmunology.


      PubDate: 2014-10-12T04:08:23Z
       
  • Bone and fat: A relationship of different shades
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Beata Lecka-Czernik , Lance A. Stechschulte
      Environmental and behavioral changes which occurred over the last century led simultaneously to a remarkable increase in human lifespan and to the development of health problems associated with functional impairment of organs either regulating or dependent on balanced energy metabolism. Diseases such as diabetes, obesity and osteoporosis are prevalent in our society and pose major challenges with respect to the overall health and economy. Therefore, better understanding of regulatory axes between bone and fat may provide the basis for development of strategies which will treat these diseases simultaneously and improve health and life quality of elderly.


      PubDate: 2014-10-12T04:08:23Z
       
  • Central genes, pathways and modules that regulate bone mass
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Isabel Quiros-Gonzalez , Vijay K. Yadav
      Bones are structures that give the shape and defined features to vertebrates, protect several soft organs and perform multiple endocrine influences on other organs. To achieve these functions bones are first modeled early during life and then constantly remodeled throughout life. The process of bone (re)modeling happens simultaneously at multitude of locations in the skeleton and ensures that vertebrates have a mechanically strong yet a flexible skeleton to the most part of their life. Given the extent of its occurrence in the body, bone remodeling is a highly energy demanding process and is co-ordinated with other physiological processes as diverse as energy metabolism, sleep–wake cycle and reproduction. Neuronal circuits in the brain play a very important role in the coordination of bone remodeling with other organ system functions, and perform this function in sync with environmental and peripheral hormonal cues. In this review, we will focus on the roles of hormonal signals and neural circuits that originate in, or impinge on, the brain in the regulation of bone mass. We will provide herein an updated view of how advances in molecular genetics have refined the neural circuits involved in the regulation of bone mass, from the whole brain level to the specific neuronal populations and their neurotransmitters. This will help to understand the mechanisms whereby vertebrate brain regulates bone mass by fine-tuning metabolic signals that originate in the brain or elsewhere in the body.


      PubDate: 2014-10-12T04:08:23Z
       
  • Regulation of energy metabolism by the skeleton: Osteocalcin and beyond
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Mathieu Ferron , Julie Lacombe
      The skeleton has recently emerged as an endocrine organ implicated in the regulation of glucose and energy metabolism. This function of bone is mediated, at least in part, by osteocalcin, an osteoblast-derived protein acting as a hormone stimulating insulin sensitivity, insulin secretion and energy expenditure. Osteocalcin secretion and bioactivity is in turn regulated by several hormonal cues including insulin, leptin, the sympathetic nervous system and glucocorticoids. Recent findings support the notion that osteocalcin functions and regulations are conserved between mice and humans. Moreover, studies in mice suggest that osteocalcin could represent a viable therapeutic approach for the treatment of obesity and insulin resistance. In this review, we summarize the current knowledge on osteocalcin functions, its various modes of action and the mechanisms implicated in the control of this hormone.


      PubDate: 2014-10-12T04:08:23Z
       
  • Reciprocal interaction between bone and gonads
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Alexandre Chamouni , Franck Oury
      The demonstration that the skeleton is an endocrine organ has enriched the physiological importance of this tissue and advanced our understanding of whole-organism homeostasis. Moreover, that bone affects powerful regulators of its own physiology such as glucose metabolism, energy expenditure, gonads and brain, reinforced the concept of interdependence between organs. This notion is particularly true for the interplay between bone and gonads. On one hand, gonads are essential for bone growth, maturation and maintenance via the secretion of the sex steroid hormones. On the other hand, bone returns this favor to the gonads, through the secretion of osteocalcin (Ocn), which promotes testosterone biosynthesis following its binding to Gprc6a, a G-protein-coupled receptor. Moreover, that a loss of function mutation in GPRC6A leads to glucose intolerance and male sterility in human, expands the biological relevance of the endocrine role of the skeleton and suggests to some extent its implication in the onset of reproductive and metabolic human diseases.


      PubDate: 2014-10-12T04:08:23Z
       
  • Bone–kidney axis in systemic phosphate turnover
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Mohammed Shawkat Razzaque
      An adequate phosphate balance is essential for the maintenance of skeletal growth, development and function. It is also crucial in basic cellular functions, ranging from cell signaling to energy metabolism. Bone-derived fibroblast growth factor 23 (FGF23), through activating FGF receptor system, plays an important role in the systemic regulation of phosphate metabolism. Under physiological conditions, FGF23 exerts serum phosphate-lowering effects by inducing urinary phosphate excretion. Increased FGF23 activities are associated with hypophosphatemic diseases (i.e., rickets/osteomalacia), while reduced FGF23 activity are linked to hyperphosphatemic diseases (i.e., tumoral calcinosis). Unlike most of the FGF family members, FGF23 needs klotho, as a co-factor to activate its receptor system. In vivo studies have convincingly demonstrated that, in absence of klotho, FGF23 is unable to influence systemic phosphate metabolism. Available information suggests that interactions of FGF23, klotho, and FGFRs regulate renal phosphate metabolism by suppressing sodium-phosphate transporters in the proximal tubular epithelial cells. This article briefly summarizes how bone–kidney communication contributes to physiologic phosphate balance.


      PubDate: 2014-10-12T04:08:23Z
       
  • Cancer and bone: A complex complex
    • Abstract: Publication date: 1 November 2014
      Source:Archives of Biochemistry and Biophysics, Volume 561
      Author(s): Marjolein van Driel , Johannes P.T.M. van Leeuwen
      Primary and secondary bone cancers are rare events. However, once settled, a complex process is started involving an extensive amount of factors and interactions. The bone micro-environment is a preferential site for (metastatic) tumor cells to enter, stay, colonize and expand. The fact that the tumor cells affect the complete bone environment involving many cell types and regulatory pathways to stimulate their own growth and escape from therapy is devastating for the patient. Many efforts have been made to get more insight into the mechanisms underlying the communication between bone cells and cancer cells and progress is made in therapeutic interventions. This review will discuss the biological mechanisms of primary bone malignancies (osteosarcoma, Ewing’s sarcoma, chondrosarcoma, multiple myeloma) and secondary bone malignancies (bone metastases) and therapeutic interventions.


      PubDate: 2014-10-12T04:08:23Z
       
  • Investigation on the influence of
           (Z)-3-(2-(3-chlorophenyl)hydrazono)-5,6-dihydroxyindolin-2-one (PT2) on
           β-amyloid(1–40) aggregation and toxicity
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Marco Catto , Fabio Arnesano , Gerardo Palazzo , Angelo De Stradis , Vincenza Calò , Maurizio Losacco , Rosa Purgatorio , Francesco Campagna
      In Alzheimer’s disease (AD), native Aβ protein monomers aggregate through the formation of a variety of water-soluble, toxic oligomers, ultimately leading to insoluble fibrillar deposits. The inhibition of oligomers formation and/or their dissociation into non-toxic monomers, are considered an attractive strategy for the prevention and treatment of AD. A number of studies have demonstrated that small molecules, containing single or multiple (hetero)aromatic rings, can inhibit protein aggregation, being potentially effective in AD treatment. Starting from previously reported data on the antiamyloidogenic activity of a series of 3-hydrazonoindolinones, compound PT2 was selected to deeply investigate the inhibitory mechanism in the Aβ aggregation cascade. We compared data from DLS, NMR, CD, TEM and ThT fluorescence measures to ascertain the interactions with amyloidogenic species formed in vitro during the aggregation process, and confirmed this feature with cell viability tests on HeLa cultured cells. PT2 was effective in disrupting toxic oligomers and mature amyloid fibrils, stabilizing Aβ as non-toxic, β-sheet arranged, ThT-insensitive protofilaments. It also strongly reduced cellular toxicity caused by Aβ and showed good antioxidant properties in two radical scavenging tests. Taken together, these data confirmed that PT2 is a small molecule inhibitor of Aβ oligomerization and toxicity, displaying also additional activity as antioxidant.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • G-quadruplex formation of FXYD1 pre-mRNA indicates the possibility of
           regulating expression of its protein product
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Hansraj Dhayan , Anwar R. Baydoun , Andreas Kukol
      G-quadruplexes are higher-order nucleic acid structures formed of square-planar arrangements of four guanine bases held together by Hoogsteen-type hydrogen bonds. Stacks of guanine tetrads are stabilised by intercalating potassium ions. FXYD1 encodes for phospholemman, a regulatory subunit of the cardiac Na+/K+-ATPase. Computational sequence analysis of FXYD1 pre-mRNA predicted the formation of stable intramolecular G-quadruplexes in human and orthologue sequences. Multiple sequence alignment indicated that G-rich sequences are conserved in evolution suggesting a potential role of G-quadruplexes in FXYD1 gene expression. The existence of a non-functional alternative splicing product indicated that the G-quadruplex formation may control alternative splicing. Quadruplex formation of human and bovine oligonucleotides was confirmed in vitro by native polyacrylamide gel electrophoresis and intrinsic fluorescence emission spectroscopy. Taking together the evolutionary conservation of G-quadruplex forming sequences with the confirmation of G-quadruplex formation in vitro by two FXYD1 homologues the results point to a potential role of these structures in regulating the expression of FXYD1 and thus regulate indirectly the activity of the cardiac Na+/K+-ATPase.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Expression of organic osmolyte transporters in cultured rat astrocytes and
           rat and human cerebral cortex
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Jessica Oenarto , Boris Görg , Michael Moos , Hans-Jürgen Bidmon , Dieter Häussinger
      This study characterizes the expression of the osmolyte transporters betaine/γ-amino-n-butyric acid (GABA) transporter (BGT-1), the taurine transporter (TauT) and the sodium-dependent myo-inositol transporter (SMIT) in various rat brain cells in culture and in rat and human cerebral cortex in situ. Osmolyte transporter expression greatly differed between cultured brain cells with highest mRNA expression levels for SMIT in astrocytes and TauT in neurons. BGT-1 mRNA and protein were expressed in microglia but not in astrocytes and neurons. In rat and human cerebral cortex, SMIT was expressed in astrocytes and TauT was found in neurons. Osmolyte transporter expression was subject to regulation by factors relevant for hepatic encephalopathy (HE). Hypoosmolarity, NH4Cl (0.5–5mmol/l), diazepam (10μmol/l) and TNFα (10ng/ml) time-dependently decreased mRNA expression of SMIT and/or TauT in cultured astrocytes. NH4Cl-induced SMIT/TauT mRNA expression changes were sensitive to inhibitors of glutamine synthetase and NADPH oxidase. In rat cerebral cortex, SMIT mRNA expression decreased after portal vein ligation or ammonium acetate injection probably due to astrocyte swelling in these HE animal models. It is concluded that osmolyte transporters are heterogeneously expressed in brain and are subject to regulation by HE-relevant factors.


      PubDate: 2014-09-01T22:27:55Z
       
  • Low-molecular-weight thiols in plants: Functional and analytical
           implications
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Micaela Pivato , Marta Fabrega-Prats , Antonio Masi
      Low-molecular-weight (LMW) thiols are a class of highly reactive compounds massively involved in the maintenance of cellular redox homeostasis. They are implicated in plant responses to almost all stress factors, as well as in the regulation of cellular metabolism. The most studied LMW thiols are glutathione and its biosynthetically related compounds (cysteine, γ-glutamylcysteine, cysteinylglycine, and phytochelatins). Other LMW thiols are described in the literature, such as thiocysteine, cysteamine, homocysteine, lipoic acid, and many species-specific volatile thiols. Here, we review the known LMW thiols in plants, briefly describing their physico-chemical properties, their relevance in post-translational protein modification, and recently-developed thiol detection methods. Current research points to a huge thiol biodiversity in plants and many species-specific and organ-specific thiols remain to be identified. Recent advances in technology should help researchers in this very challenging task, helping us to decipher the roles of thiols in plant metabolism.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Atmospheric-pressure plasma jet induces DNA double-strand breaks that
           require a Rad51-mediated homologous recombination for repair in
           Saccharomyces cerevisiae
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Yoonna Lee , Kangil Kim , Kyu-Tae Kang , Jong-Soo Lee , Sang Sik Yang , Woo-Hyun Chung
      Non-thermal plasma generated under atmospheric pressure produces a mixture of chemically reactive molecules and has been developed for a number of biomedical applications. Recently, plasma jet has been proposed as novel cancer therapies based on the observation that free radicals generated by plasma jet induce mitochondria-mediated apoptotic cell death. We show here that air plasma jet induces DNA double-strand breaks (DSBs) in yeast chromosomes leading to genomic instability and loss of viability, which are alleviated by Rad51, the yeast homolog of E scherichia coli RecA recombinase, through DNA damage repair by a homologous recombination (HR) process. Hypersensitivity of rad51 mutant to air plasma was not restored by antioxidant treatment unlike sod1 mutant that was highly sensitive to reactive oxygen species (ROS) challenge, suggesting that plasma jet induces DSB-mediated cell death independent of ROS generation. These results may provide a new insight into the mechanism of air plasma jet-induced cell death.


      PubDate: 2014-09-01T22:27:55Z
       
  • Structural and biochemical analysis of a type II free
           methionine-R-sulfoxide reductase from Thermoplasma acidophilum
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Hyun Sook Kim , Geun-Hee Kwak , Kitaik Lee , Chang-Hwa Jo , Kwang Yeon Hwang , Hwa-Young Kim
      Free methionine-R-sulfoxide reductase (fRMsr) enzymes only reduce the free form of methionine-R-sulfoxide and can be grouped into two types with respect to the number of conserved Cys residues in the active sites. In this work, the crystal structures of type II fRMsr from Thermoplasma acidophilum (TafRMsr), which contains two conserved Cys, have been determined in native form and in a complex with the substrate. The overall structure of TafRMsr consists of a central β-sheet encompassed by a two-α-helix bundle flanking on one side and one small α-helix on the other side. Based on biochemical and growth complementation assays, Cys84 is demonstrated to be the catalytic Cys. The data also show that TafRMsr functions as an antioxidant protein. Structural analyses reveal insights into substrate recognition and orientation, conformational changes in the active site during substrate binding, and the role of active site residues in substrate binding. A model for the catalytic mechanism of type II TafRMsr is suggested, in which intramolecular disulfide bond formation is not involved. In addition, the biochemical, enzymatic, and structural properties of type II TafRMsr are compared with those of type I enzymes.


      PubDate: 2014-09-01T22:27:55Z
       
  • High-glucose-induced CARM1 expression regulates apoptosis of human retinal
           pigment epithelial cells via histone 3 arginine 17 dimethylation: Role in
           diabetic retinopathy
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Dong-il Kim , Min-jung Park , Seul-ki Lim , Joo-hee Choi , Jong-choon Kim , Ho-jae Han , Tapas K. Kundu , Jae-il Park , Kyung-chul Yoon , Sang-woo Park , Jong-sung Park , Young-ran Heo , Soo-hyun Park
      Hyperglycemia-induced apoptosis of retinal pigment epithelial (RPE) cells is considered to be involved in the progression of diabetic retinopathy. Histone arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has emerged as an important histone modification involved in gene regulation. However, the role of PRMTs in diabetic retinopathy has not been elucidated. Here, we found that expression of coactivator-associated arginine methyltransferase 1 (CARM1; also known as PRMT4) was increased in the high-glucose treated human RPE cell line ARPE-19 and in the RPE layer of streptozotocin-treated rats. In addition, high-glucose induced apoptosis in ARPE-19 cells. To determine the function of CARM1 on RPE cell apoptosis, we performed gain- and loss-of-function studies. CARM1 overexpression increased apoptosis of RPE cells. In contrast, silencing of CARM1 expression by siRNA and pharmacological inhibition of CARM1 activity abolished high-glucose-induced RPE cell apoptosis. Furthermore, we found that inhibition of histone 3 arginine 17 (H3R17) asymmetric dimethylation attenuates both CARM1- and high-glucose-induced apoptosis in RPE cells. Together, these results show that high-glucose-induced CARM1 expression increases RPE cell apoptosis via H3R17 asymmetric dimethylation. Strategies to reduce CARM1 expression or enzymatic activity could be used to prevent apoptosis of RPE cells in the progression of diabetic retinopathy.


      PubDate: 2014-09-01T22:27:55Z
       
  • Disrupted calcium homeostasis is involved in elevated zinc ion-induced
           photoreceptor cell death
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Dadong Guo , Yuxiang Du , Qiuxin Wu , Wenjun Jiang , Hongsheng Bi
      Zinc (Zn), the second abundant trace element in living organisms, plays an important role in regulating cell metabolism, signaling, proliferation, gene expression and apoptosis. Meanwhile, the overload of Zn will disrupt the intracellular calcium homeostasis via impairing mitochondrial function. However, the specific molecular mechanism underlying zinc-induced calcium regulation remains poorly understood. In the present study, using zinc chloride (ZnCl2) as a stressor, we investigated the effect of exogenous Zn2+ in regulating murine photoreceptor cell viability, reactive oxygen species (ROS), cell cycle distribution and calcium homeostasis as well as plasma membrane calcium ATPase (PMCA) isoforms (PMCA1 and PMCA2, i.e., ATP2B1, ATP2B2) expression. We found that the exogenous Zn2+ in the exposure range (31.25–125.0μmol/L) results in the overgeneration of ROS, cell cycle arrest at G2/M phases, elevation of cytosolic [Ca2+], inactivation of Ca2+-ATPase and reduction of both PMCA1 and PMCA2 in 661Wcells, and thus induces cell death. In conclusion, ZnCl2 exposure can elevate the cytosolic [Ca2+], disrupt the intracellular calcium homeostasis, further initiate Ca2+-dependent signaling pathway in 661Wcells, and finally cause cell death. Our results will facilitate the understanding of cell death induced by the zinc ion-mediated calcium homeostasis disruption.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Dynamic profile and adipogenic role of growth differentiation factor 5
           (GDF5) in the differentiation of 3T3-L1 preadipocytes
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Zhou Pei , Yi Yang , Wieland Kiess , Chengjun Sun , Feihong Luo
      Adipocyte differentiation is key to determining the number of adipocytes during the development of obesity. Recent studies have shown that growth differentiation factor-5 (GDF5) promotes brown adipogenesis, however its role in white adipogenesis is still uncertain. The aim of the present study was to investigate the effect of GDF5 on white adipogenesis using 3T3-L1 preadipocyte model. In the present study, GDF5 was found to be differentially regulated during adipocyte differentiation. GDF5 protein increased the differentiation of 3T3-L1 preadipocytes, especially when these cells were exposed to hormone cocktails without insulin. During adipogenesis, GDF5 enhanced the expression of genes related to adipocyte differentiation and caused cells to enter the S phase. Short-hairpin-RNA knockdown of GDF5 in 3T3-L1 cells was found to prevent adipogenesis induced by a standard hormone cocktail and to downregulate the expression of adipocyte genes and proteins, this impairment could be partly rescued by GDF5 protein. Collectively, these results suggest that GDF5 can promote progression of the cell-cycle and increase numbers of cells in S phase, GDF5 might play a critical role in 3T3-L1 preadipocyte differentiation.


      PubDate: 2014-09-01T22:27:55Z
       
  • Inhibition of Escherichia coli tryptophan indole-lyase by tryptophan
           homologues
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Quang T. Do , Giang T. Nguyen , Victor Celis , Robert S. Phillips
      We have designed, synthesized and evaluated homotryptophan analogues as possible mechanism-based inhibitors for Escherichia coli tryptophan indole-lyase (tryptophanase, TIL, E.C. 4.1.99.1). As a quinonoid structure is an intermediate in the reaction mechanism of TIL, we anticipated that homologation of the physiological substrate, l-Trp would provide analogues resembling the transition state for β-elimination, and potentially inhibit TIL. Our results demonstrate that l-homotryptophan (1a) is a moderate competitive inhibitor of TIL, with Ki =67μM, whereas l-bishomotryptophan (1b) displays more potent inhibition, with Ki =4.7μM. Pre-steady-state kinetics indicated the formation of an external aldimine and quinonoid with 1a, but only the formation of an external aldimine for 1b, suggesting differences in the inhibition mechanism. These results demonstrate that formation of a quinonoid complex is not required for strong inhibition. In addition, the Trp analogues were evaluated as inhibitors of Salmonella typhimurium Trp synthase. Our results indicate that compound 1b is at least 25-fold more selective toward TIL than Trp synthase. We report that compound 1b is comparable to the most potent inhibitor previously reported, while displaying high selectivity for TIL. Thus, 1b is a potential lead for the development of novel antibacterials.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
 
 
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