for Journals by Title or ISSN
for Articles by Keywords
help
  Subjects -> BIOLOGY (Total: 2664 journals)
    - BIOCHEMISTRY (204 journals)
    - BIOENGINEERING (71 journals)
    - BIOLOGY (1338 journals)
    - BIOPHYSICS (43 journals)
    - BIOTECHNOLOGY (150 journals)
    - BOTANY (200 journals)
    - CYTOLOGY AND HISTOLOGY (24 journals)
    - ENTOMOLOGY (54 journals)
    - GENETICS (137 journals)
    - MICROBIOLOGY (221 journals)
    - MICROSCOPY (9 journals)
    - ORNITHOLOGY (23 journals)
    - PHYSIOLOGY (66 journals)
    - ZOOLOGY (124 journals)

BIOCHEMISTRY (204 journals)                  1 2 3     

AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Chemical Biology     Full-text available via subscription   (Followers: 308)
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: 179)
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: 206)
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: 17)
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)
Asian Journal of Biomedical and Pharmaceutical Sciences     Open Access  
Avicenna Journal of Medical Biochemistry     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 3)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 14)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 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: 3)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 222)
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: 20)
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: 5)
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)

        1 2 3     

Journal Cover Archives of Biochemistry and Biophysics
   [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  [2571 journals]   [SJR: 1.131]   [H-I: 115]
  • Leukotriene signaling in the extinct human subspecies Homo denisovan and
           Homo neanderthalensis. Structural and functional comparison with Homo
           sapiens
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): Susan Adel , Kumar Reddy Kakularam , Thomas Horn , Pallu Reddanna , Hartmut Kuhn , Dagmar Heydeck
      Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies.
      Graphical abstract image

      PubDate: 2014-11-23T08:23:27Z
       
  • Isolation and characterization of a protease inhibitor from Acacia karroo
           with a common combining loop and overlapping binding sites for
           chymotrypsin and trypsin
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): András Patthy , Tamás Molnár , Pálma Porrogi , Ryno Naudé , László Gráf
      By using affinity and reversed-phase HPLC (RP-HPLC) chromatographies two chymotrypsin–trypsin inhibitors were isolated from seeds of Acacia karroo, a legume of the subfamily Mimosoideae. The primary structure of one of these inhibitors, named AkCI/1, was determined. The inhibitor consists of two polypeptide chains, 139 and 44 residues respectively, which are linked by a single disulfide bridge. The amino acid sequence of AkCI/1 is homologous to and showed more than 60% sequence similarity with other protease inhibitors isolated earlier from the group of Mimosoideae. AkCI/1 inhibits both chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) in a 1:1M ratio with K i values of 2.8×10−12 M and 1.87×10−12 M, respectively. The P1–P1′ residues for trypsin were identified as Arg68-Ile69 by selective hydrolysis of the inhibitor at this site, with bovine trypsin and human trypsin IV. The cleavage did not affect the inhibition of trypsin, but fully abolished the chymotrypsin inhibitory activity of AkCI/1. This finding together with our studies on competition of the two enzymes for the same combining loop suggests that the same loop has to contain the binding sites for both proteases. The most likely P1 residue of AkCI/1 for chymotrypsin is Tyr67.


      PubDate: 2014-11-23T08:23:27Z
       
  • Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular
           signaling pathway in human hepatocellular carcinoma cells
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): Tomoaki Nagasawa , Rie Matsushima-Nishiwaki , Eisuke Yasuda , Junya Matsuura , Hidenori Toyoda , Yuji Kaneoka , Takashi Kumada , Osamu Kozawa
      We previously demonstrated that the expression of HSP20, a small heat shock protein, is inversely correlated with the progression of HCC. Inflammation is associated with HCC, and numerous cytokines, including TNF-α, act as key mediators in the progression of HCC. In the present study, we investigated whether HSP20 is implicated in the TNF-α-stimulated intracellular signaling in HCC using human HCC-derived HuH7 cells in the presence of TNF-α. In HSP20-overexpressing HCC cells, the cell growth was retarded compared with that in the control cells under long-term exposure of TNF-α. Because NF-κB pathway is the main intracellular signaling system activated by TNF-α, we investigated the effects of HSP20-overexpression of this pathway. The protein levels of IKK-α, but not IKK-β, in the HSP20-overexpressing cells were decreased. Short-term exposure to TNF-α-induced phosphorylation and degradation of IκB, and the phosphorylation and transactivational activity of NF-κB were suppressed in the HSP20-overexpressing HCC cells. Furthermore, the increase in IKK-α levels was accompanied by a decrease in the HSP20 levels in human HCC tissues. These findings strongly suggest that HSP20 might decrease the IKK-α protein level and that it down-regulates the TNF-α-stimulated intracellular signaling in HCC, thus resulting in the suppression of HCC progression.


      PubDate: 2014-11-20T08:08:41Z
       
  • Targeting prion propagation using peptide constructs with signal sequence
           motifs
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Kajsa Löfgren Söderberg , Peter Guterstam , Ülo Langel , Astrid Gräslund
      Synthetic peptides with sequences derived from the cellular prion protein (PrPC) unprocessed N-terminus are able to counteract the propagation of proteinase K resistant prions (PrPRes, indicating the presence of the prion isoform of the prion protein) in cell cultures (Löfgren et al., 2008). The anti-prion peptides have characteristics like cell penetrating peptides (CPPs) and consist of the prion protein hydrophobic signal sequence followed by a polycationic motif (residues KKRPKP), in mouse PrPC corresponding to residues 1–28. Here we analyze the sequence elements required for the anti-prion effect of KKRPKP-conjugates. Neuronal GT1-1 cells were infected with either prion strain RML or 22L. Variable peptide constructs originating from the mPrP1 – 28 sequence were analyzed for anti-prion effects, measured as disappearance of proteinase K resistant prions (PrPRes) in the infected cell cultures. We find that even a 5 amino acid N-terminal shortening of the signal peptide abolishes the anti-prion effect. We show that the signal peptide from PrPC can be replaced with the signal peptide from the Neural cell adhesion molecule-1; NCAM11 – 19, with a retained capacity to reduce PrPRes levels. The anti-prion effect is lost if the polycationic N-terminal PrPC-motif is conjugated to any conventional CPP, such as TAT48–60, transportan-10 or penetratin. We propose a mechanism by which a signal peptide from a secretory or cell surface protein acts to promote the transport of a prion-binding polycationic PrPC-motif to a subcellular location where prion conversion occurs (most likely the Endosome Recycling Compartment), thereby targeting prion propagation.


      PubDate: 2014-11-16T07:51:37Z
       
  • Multiple UDP-glucuronosyltransferases in human liver microsomes
           glucuronidate both R- and S-7-hydroxywarfarin into two metabolites
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      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: 2014-11-11T07:36:24Z
       
  • Site-directed mutagenesis of the highly perturbed copper site of
           auracyanin D
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Jeremy D. King , Lucas Harrington , Bryan M. Lada , Guannan He , Jason W. Cooley , Robert E. Blankenship
      Type-1 copper proteins participate in redox reactions and biological catalysis. Significant variation exists within the electronic structure of type-1 copper sites, producing both blue and green proteins. Classical, “blue” sites have been extensively studied, but “green” sites have been poorly characterized. We recently discovered a green copper protein, called auracyanin D. Here, we report a series of axial ligand mutations in auracyanin D, and characterize the resulting spectral and redox changes. The resulting mutants appear blue, green, and red and vary in redox potential from +56mV to +786mV. This is the largest change in redox potential to date for any type-1 center. We found that in this green protein, modifications of the axial ligand produce significantly larger changes than similar mutations in blue type-1 copper sites.


      PubDate: 2014-11-08T07:24:43Z
       
  • Interaction of ERK1/2 and Smad2/3 signaling pathways in
           TGF-β1-induced TIMP-3 expression in rat chondrocytes
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Xiang Wang , Yanhui Zhu , Hairong Tao , Chen Jin , Yonzhang Liu , Xiongwei Lu , Xiaopeng Hu , Cunyi Fan
      Tissue inhibitor of metalloproteinase-3 (TIMP-3) is an important natural inhibitor of matrix metalloproteinases (MMPs) and of a disintegrin and metalloproteinase with thrombospondin motif (ADAMTs), which can cleave cartilage extracellular matrix components to cause cartilage degradation. In this study, our data suggest TGF-β1 induces TIMP-3 expression through activations of both the ERK1/2 and Smad2/3 signaling pathways. TGF-β1-stimulated TIMP-3 expression was significantly inhibited by SB525334 (TGF-β receptor I kinase inhibitor), accompanied by a reduction in ERK1/2 and Smad3 phosphorylation. We used PD98059 (MEK inhibitor) and SIS3 (inhibitor of Smad3 phosphorylation) to investigate the respective roles of ERK1/2 and Smad2/3 signaling pathways in TGF-β1-induced TIMP-3 expression. The results show PD98059 treatment significantly suppressed TGF-β1-induced ERK1/2 phosphorylation and TIMP-3 expression. Under these conditions, the degree of Smad3 phosphorylation correlated with ERK1/2 activation, which suggests that ERK1/2 may activate Smad3 phosphorylation. SIS3 significantly inhibited TGF-β1-induced Smad3 phosphorylation and TIMP-3 expression. ERK1/2 phosphorylation alone had no effect on TGF-β1-induced TIMP-3 expression, which suggests ERK1/2 via Smad3 phosphorylation regulates TGF-β1-induced TIMP-3 expression. Here, we demonstrate that ERK1/2 may be capable of activating the Smad2/3 signaling pathway to result in TGF-β1-induced TIMP-3 up-regulation.


      PubDate: 2014-11-08T07:24:43Z
       
  • The roles of microphthalmia-associated transcription factor and
           pigmentation in melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Jennifer J. Hsiao , David E. Fisher
      MITF and pigmentation play important roles in both normal melanocyte and transformed melanoma cell biology. MITF is regulated by many pathways and it also regulates many targets, some of which are still being discovered and functionally validated. MITF is involved in a wide range of processes in melanocytes, including pigment synthesis and lineage survival. Pigmentation itself plays an important role as the interface between genetic and environmental factors that contribute to melanoma.


      PubDate: 2014-11-04T07:16:29Z
       
  • Ion transport in pigmentation
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Nicholas W. Bellono , Elena V. Oancea
      Skin melanocytes and ocular pigment cells contain specialized organelles called melanosomes, which are responsible for the synthesis of melanin, the major pigment in mammals. Defects in the complex mechanisms involved in melanin synthesis and regulation result in vision and pigmentation deficits, impaired development of the visual system, and increased susceptibility to skin and eye cancers. Ion transport across cellular membranes is critical for many biological processes, including pigmentation, but the molecular mechanisms by which it regulates melanin synthesis, storage, and transfer are not understood. In this review we first discuss ion channels and transporters that function at the plasma membrane of melanocytes; in the second part we consider ion transport across the membrane of intracellular organelles, with emphasis on melanosomes. We discuss recently characterized lysosomal and endosomal ion channels and transporters associated with pigmentation phenotypes. We then review the evidence for melanosomal channels and transporters critical for pigmentation, discussing potential molecular mechanisms mediating their function. The studies investigating ion transport in pigmentation physiology open new avenues for future research and could reveal novel molecular mechanisms underlying melanogenesis.
      Graphical abstract image

      PubDate: 2014-11-04T07:16:29Z
       
  • The contribution of activating transcription factor 3 to apoptosis of
           human colorectal cancer cells by protocatechualdehyde, a naturally
           occurring phenolic compound
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      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: 2014-11-04T07:16:29Z
       
  • Developmental pathways activated in melanocytes and melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Jianglan Liu , Mizuho Fukunaga-Kalabis , Ling Li , Meenhard Herlyn
      Cutaneous malignant melanomas originate primarily within epidermal melanocytic cells. Melanoma cells share many characteristics with melanocyte precursors, suggesting that melanoma cells utilize the developmental programs of their normal counterpart for their own progression. The pigmentation system provides an advantageous model to assess survival pathway interactions in the melanocytic lineage, as genetic alterations controlling melanocyte development can be easily detectable by coat color phenotype that do not affect the viability of an animal. By integrating combinatorial gene knockout approaches, cell-based assays and immunohistochemical observations, recent studies have illustrated several genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. We are reviewing those genes and pathways to understand the connection between normal and cancerous development and to reveal therapeutic potential of targeting developmental pathways for melanoma therapy.


      PubDate: 2014-11-04T07:16:29Z
       
  • Cyclic AMP (cAMP) signaling in melanocytes and melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Carlos Iván Rodríguez , Vijayasaradhi Setaluri
      G-protein coupled receptors (GPCRs), which include melanocortin-1 receptor (MC1R), play a crucial role in melanocytes development, proliferation and differentiation. Activation of the MC1R by the α-melanocyte stimulating hormone (α-MSH) leads to the activation of the cAMP signaling pathway that is mainly associated with differentiation and pigment production. Some MC1R polymorphisms produce cAMP signaling impairment and pigmentary phenotypes such as the red head color and fair skin phenotype (RHC) that is usually associated with higher risk for melanoma development. Despite its importance in melanocyte biology, the role of cAMP signaling cutaneous melanoma is not well understood. Melanoma is primarily driven by mutations in the components of mitogen-activated protein kinases (MAPK) pathway. Increasing evidence, however, now suggests that cAMP signaling also plays an important role in melanoma even though genetic alterations in components of this pathway are note commonly found in melanoma. Here we review these new roles for cAMP in melanoma including its contribution to the notorious treatment resistance of melanoma.


      PubDate: 2014-11-04T07:16:29Z
       
  • Advances in melanocyte and melanoma biology
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Hasan Mukhtar , Vijayasaradhi Setaluri



      PubDate: 2014-11-04T07:16:29Z
       
  • Melanocortins and the melanocortin 1 receptor, moving translationally
           towards melanoma prevention
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Zalfa A. Abdel-Malek , Viki B. Swope , Renny J. Starner , Leonid Koikov , Pamela Cassidy , Sancy Leachman
      Beginning in the last decade of the twentieth century, the fields of pigment cell research and melanoma have witnessed major breakthroughs in the understanding of the role of melanocortins in human pigmentation and the DNA damage response of human melanocytes to solar ultraviolet radiation (UV). This began with the cloning of the melanocortin 1 receptor (MC1R) gene from human melanocytes and the demonstration that the encoded receptor is functional. Subsequently, population studies found that the MC1R gene is highly polymorphic, and that some of its variants are associated with red hair phenotype, fair skin and poor tanning ability. Using human melanocytes cultured from donors with different MC1R genotypes revealed that the alleles associated with red hair color encode for a non-functional receptor. Epidemiological studies linked the MC1R red hair color variants to increased melanoma risk. Investigating the impact of different MC1R variants on the response of human melanocytes to UV led to the important discovery that the MC1R signaling activates antioxidant, DNA repair and survival pathways, in addition to stimulation of eumelanin synthesis. These effects of MC1R were absent in melanocytes expressing 2 MC1R red hair color variants that result in loss of function of the receptor. The importance of the MC1R in reducing UV-induced genotoxicity in melanocytes led us to design small peptide analogs of the physiological MC1R agonist α-melanocortin (α-melanocyte stimulating hormone; α-MSH) for the goal of utilizing them for melanoma chemoprevention.


      PubDate: 2014-11-04T07:16:29Z
       
  • microRNA-340 as a modulator of RAS–RAF–MAPK signaling in
           melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Ashley M. Poenitzsch Strong , Vijayasaradhi Setaluri , Vladimir S. Spiegelman
      microRNA (miRNA)-dependent regulation of gene expression is increasingly linked to development and progression of melanoma. In this study we evaluated the functions of miR-340 in human melanoma cells. Here, we show that miR-340 inhibits the tumorigenic phenotype of melanoma cells. We also found that miR-340 regulates RAS–RAF–Mitogen Activated Protein Kinase (MAPK) signaling by modulating the expression of multiple components of this pathway. Given the importance of MAPK signaling in melanoma, these results provide further insight into the pathogenesis of melanoma.


      PubDate: 2014-11-04T07:16:29Z
       
  • Modulation of BRAHMA expression by the mitogen-activated protein
           kinase/extracellular signal regulated kinase pathway is associated with
           changes in melanoma proliferation
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Aanchal Mehrotra , Srinivas Vinod Saladi , Archit R. Trivedi , Shweta Aras , Huiling Qi , Ashika Jayanthy , Vijayasaradhi Setaluri , Ivana L. de la Serna
      Brahma (BRM) and Brahma-related gene 1(BRG1) are catalytic subunits of SWItch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complexes. BRM is epigenetically silenced in a wide-range of tumors. Mutations in the v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene occur frequently in melanoma and lead to constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK1/2) pathway. We tested the hypothesis that BRM expression is modulated by oncogenic BRAF and phosphorylation of ERK1/2 in melanocytes and melanoma cells. Expression of oncogenic BRAF in melanocytes and melanoma cells that are wild-type for BRAF decreased BRM expression and increased BRG1 expression. Inhibition of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) or selective inhibition of BRAF in melanoma cells that harbor oncogenic BRAF increased BRM expression and decreased BRG1 expression. Increased BRM expression was associated with increased histone acetylation on the BRM promoter. Over-expression of BRM in melanoma cells that harbor oncogenic BRAF promoted changes in cell cycle progression and apoptosis consistent with a tumor suppressive role. Upon inhibition of BRAF(V600E) with PLX4032, BRM promoted survival. PLX4032 induced changes in BRM function were correlated with increased acetylation of the BRM protein. This study provides insights into the epigenetic consequences of inhibiting oncogenic BRAF in melanoma through modulation of SWI/SNF subunit expression and function.


      PubDate: 2014-11-04T07:16:29Z
       
  • Involvement of ER stress and activation of apoptotic pathways in fisetin
           induced cytotoxicity in human melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Deeba N. Syed , Rahul K. Lall , Jean Christopher Chamcheu , Omar Haidar , Hasan Mukhtar
      The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytotoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up-regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMP-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.


      PubDate: 2014-11-04T07:16:29Z
       
  • Methotrexate inhibits the viability of human melanoma cell lines and
           enhances Fas/Fas-ligand expression, apoptosis and response to
           interferon-alpha: Rationale for its use in combination therapy
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Minakshi Nihal , Jianqiang Wu , Gary S. Wood
      Melanoma, a highly aggressive form of cancer, is notoriously resistant to available therapies. Methotrexate (MTX), an antifolate, competitively inhibits DNA synthesis and is effective for several types of cancer. In cutaneous T-cell lymphoma (CTCL), MTX increases Fas death receptor by decreasing Fas promoter methylation by blocking the synthesis of SAM, the principal methyl donor for DNMTs, resulting in enhanced Fas-mediated apoptosis. The objective of this study was to explore the effects of MTX in human melanoma. MTX variably inhibited the survival of melanoma cells and induced apoptosis as evident by annexin V positivity and senescence associated β-galactosidase activity induction. Furthermore, MTX caused increased transcript and protein levels of extrinsic apoptotic pathway factors Fas and Fas-ligand, albeit at different levels in different cell lines. Our pyrosequencing studies showed that this increased expression of Fas was associated with Fas promoter demethylation. Overall, the ability of MTX to up-regulate Fas/FasL and enhance melanoma apoptosis through extrinsic as well as intrinsic pathways might make it a useful component of novel combination therapies designed to affect multiple melanoma targets simultaneously. In support of this concept, combination therapy with MTX and interferon-alpha (IFNα) induced significantly greater apoptosis in the aggressive A375 cell line than either agent alone.


      PubDate: 2014-11-04T07:16:29Z
       
  • SIRT1 deacetylase is overexpressed in human melanoma and its small
           molecule inhibition imparts anti-proliferative response via p53 activation
           
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Melissa J. Wilking , Chandra Singh , Minakshi Nihal , Weixiong Zhong , Nihal Ahmad
      Melanoma causes more deaths than any other skin cancer, and its incidence in the US continues to rise. Current medical therapies are insufficient to control this deadly neoplasm, necessitating the development of new target-based approaches. The objective of this study was to determine the role and functional significance of the class III histone deacetylase SIRT1 in melanoma. We have found that SIRT1 is overexpressed in clinical human melanoma tissues and human melanoma cell lines (Sk-Mel-2, WM35, G361, A375, and Hs294T) compared to normal skin and normal melanocytes, respectively. In addition, treatment of melanoma cell lines A375, Hs294T, and G361 with Tenovin-1, a small molecule SIRT1 inhibitor, resulted in a significant decrease in cell growth and cell viability. Further, Tenovin-1 treatment also resulted in a marked decrease in the clonogenic survival of melanoma cells. Further experiments showed that the anti-proliferative response of Tenovin-1 was accompanied by an increase in the protein as well as activity of the tumor suppressor p53. This increase in p53 activity was substantiated by an increase in the protein level of its downstream target p21. Overall, these data suggest that small molecule inhibition of SIRT1 causes anti-proliferative effects in melanoma cells. SIRT1 appears to be acting through the activity of the tumor suppressor p53, which is not mutated in the majority of melanomas. However, future detailed studies are needed to further explore the role and mechanism of SIRT1 in melanoma development and progression and its usefulness in melanoma treatment.


      PubDate: 2014-11-04T07:16:29Z
       
  • Targeting melanocyte and melanoma stem cells by
           8-hydroxy-2-dipropylaminotetralin
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Jonathan G. Bonchak , Jonathan M. Eby , Kristin A. Willenborg , David Chrobak , Steven W. Henning , Anna Krzywiec , Steven L. Johnson , I. Caroline Le Poole
      Monobenzyl ether of hydroquinone (MBEH) is cytotoxic towards melanocytes. Its treatment efficacy is limited by an inability to eradicate stem cells. By contrast, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-DPAT) affects melanocyte stem cell survival. MBEH and 8-DPAT were added to melanocytes and melanoma cells to compare cytotoxicity. Stem cell content among viable cells was determined by fluorocytometry using markers CD34, Pax3, and CD271. Immunostaining was used to identify stem cells in skin explants treated with MBEH or 8-DPAT ex vivo. Mice were exposed to MBEH or 8-DPAT and scanned for depigmentation before harvesting skin. MBEH exposure prompted a relative increase in stem cells among cultured melanocytes and melanoma cells, as treatment preferentially eliminated differentiated cells and spared the stem cells. Viability of this remaining, enriched stem cell population was however rapidly reduced by exposure to 8-DPAT within melanocyte and melanoma cell cultures. In human skin explants, the abundance of melanocyte stem cells was also visibly reduced after 8-DPAT treatment, in contrast to tissue exposed to MBEH. Meanwhile, significant depigmentation of the mouse pelage and loss of differentiated melanocytes was observed in vivo in response to topical application of MBEH, but not 8-DPAT. Prolonged application of the latter agent instead appeared to effectively reduce the abundance of melanocyte stem cells in the dermis. This furthers the idea that MBEH and 8-DPAT target complementary cell populations. Results indicate that combination treatment may demonstrate superior therapeutic activity by eliminating both differentiated and tumor initiating populations.


      PubDate: 2014-11-04T07:16:29Z
       
  • The role of melanogenesis in regulation of melanoma behavior:
           Melanogenesis leads to stimulation of HIF-1α expression and
           HIF-dependent attendant pathways
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): A. Slominski , T.-K. Kim , A.A. Brożyna , Z. Janjetovic , D.L.P. Brooks , L.P. Schwab , C. Skobowiat , W. Jóźwicki , T.N. Seagroves
      To study the effect of melanogenesis on HIF-1α expression and attendant pathways, we used stable human and hamster melanoma cell lines in which the amelanotic vs. melanotic phenotypes are dependent upon the concentration of melanogenesis precursors in the culture media. The induction of melanin pigmentation led to significant up-regulation of HIF-1α, but not HIF-2α, protein in melanized cells for both lines. Similar upregulation of nuclear HIF-1α was observed in excisions of advanced melanotic vs. amelanotic melanomas. In cultured cells, melanogenesis also significantly stimulated expression of classical HIF-1-dependent target genes involved in angiogenesis and cellular metabolism, including glucose metabolism and stimulation of activity of key enzymes in the glycolytic pathway. Several other stress related genes containing putative HRE consensus sites were also upregulated by melanogenesis, concurrently with modulation of expression of HIF-1-independent genes encoding for steroidogenic enzymes, cytokines and growth factors. Immunohistochemical studies using a large panel of pigmented lesions revealed that higher levels of HIF-1α and GLUT-1 were detected in advanced melanomas in comparison to melanocytic nevi or thin melanomas localized to the skin. However, the effects on overall or disease free survival in melanoma patients were modest or absent for GLUT-1 or for HIF-1α, respectively. In conclusion, induction of the melanogenic pathway leads to robust upregulation of HIF-1-dependent and independent pathways in cultured melanoma cells, suggesting a key role for melanogenesis in regulation of cellular metabolism.


      PubDate: 2014-11-04T07:16:29Z
       
  • Mitochondrial function in melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Nicholas Theodosakis , Goran Micevic , Daniel P. Kelly , Marcus Bosenberg
      Melanoma is the most lethal form of skin cancer and its incidence is rapidly rising. Breakthroughs in the understanding of the basic biology of melanoma in the past decade have yielded several new treatments, and advances continue to be made on a variety of fronts. One such area involves the delineation of changes in mitochondria that occur during melanoma formation, and how these changes affect responses to therapy. In this review, we summarize recent developments on the multiple functions that mitochondria play in melanoma, and how these roles are currently being evaluated as new targets for clinical intervention.


      PubDate: 2014-11-04T07:16:29Z
       
  • The role of microRNAs and long non-coding RNAs in the pathology,
           diagnosis, and management of melanoma
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Muhammad Nauman Aftab , Marcel E. Dinger , Ranjan J. Perera
      Melanoma is frequently lethal and its global incidence is steadily increasing. Despite the rapid development of different modes of targeted treatment, durable clinical responses remain elusive. A complete understanding of the molecular mechanisms that drive melanomagenesis is required, both genetic and epigenetic, in order to improve prevention, diagnosis, and treatment. There is increased appreciation of the role of microRNAs (miRNAs) in melanoma biology, including in proliferation, cell cycle, migration, invasion, and immune evasion. Data are also emerging on the role of long non-coding RNAs (lncRNAs), such as SPRY4-IT1, BANCR, and HOTAIR, in melanomagenesis. Here we review the data on the miRNAs and lncRNAs implicated in melanoma biology. An overview of these studies will be useful for providing insights into mechanisms of melanoma development and the miRNAs and lncRNAs that might be useful biomarkers or future therapeutic targets.


      PubDate: 2014-11-04T07:16:29Z
       
  • Sex disparities in melanoma outcomes: The role of biology
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Adi Nosrati , Maria L. Wei
      Melanoma outcomes differ between men and women even when adjusted for prognostic factors such as age, Breslow thickness, body site, ulceration, lymph node dissection, and for treatment, with men having poorer outcomes compared to women. The mechanisms underlying this disparity are not well understood. Behavioral differences between the sexes such as ultraviolet light exposure and health care services utilization have been suggested as contributing, and differences in endogenous biological processes such as immune function, hormonal regulation, oxidative stress response, vitamin D metabolism and sex chromosome gene expression have also been proposed as mechanisms. This review examines the cumulative evidence for biologically based processes that lead to differences in melanoma biology, including inherent sex-based differences in immune function, oxidative stress response and vitamin D metabolism; the complex interplay between sex hormones, the immune system and oxidative stress response; the effect of non-random X chromosome inactivation on tumorigenesis; and the potential contribution of recently identified oncogenes on the Y chromosome.


      PubDate: 2014-11-04T07:16:29Z
       
  • Updates of reactive oxygen species in melanoma etiology and progression
    • Abstract: Publication date: 1 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 563
      Author(s): Feng Liu-Smith , Ryan Dellinger , Frank L. Meyskens Jr.
      Reactive oxygen species (ROS) play crucial roles in all aspects of melanoma development, however, the source of ROS is not well defined. In this review we summarize recent advancement in this rapidly developing field. The cellular ROS pool in melanocytes can be derived from mitochondria, melanosomes, NADPH oxidase (NOX) family enzymes, and uncoupling of nitric oxide synthase (NOS). Current evidence suggests that Nox1, Nox4 and Nox5 are expressed in melanocytic lineage. While there is no difference in Nox1 expression levels in primary and metastatic melanoma tissues, Nox4 expression is significantly higher in a subset of metastatic melanoma tumors as compared to the primary tumors; suggesting distinct and specific signals and effects for NOX family enzymes in melanoma. Targeting these NOX enzymes using specific NOX inhibitors may be effective for a subset of certain tumors. ROS also play important roles in BRAF inhibitor induced drug resistance; hence identification and blockade of the source of this ROS may be an effective way to enhance efficacy and overcome resistance. Furthermore, ROS from different sources may interact with each other and interact with reactive nitrogen species (RNS) and drive the melanomagenesis process at all stages of disease. Further understanding ROS and RNS in melanoma etiology and progression is necessary for developing new prevention and therapeutic approaches.


      PubDate: 2014-11-04T07:16:29Z
       
  • Characterization and identification of three novel aldo–keto
           reductases from Lodderomyces elongisporus for reducing ethyl
           4-chloroacetoacetate
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      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: 2014-11-04T07:16:29Z
       
  • Cholesteryl ester diffusion, location and self-association constraints
           determine CETP activity with discoidal HDL: Excimer probe study
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      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 fulfilled 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 (0.063μMmin−1) and catalytic rate constant k cat (0.42s−1) together with a similarity of K m (0.9μM CPD) and K I (2.8μM 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: 2014-11-04T07:16:29Z
       
  • Simulated physiological stretch-induced proliferation of human bladder
           smooth muscle cells is regulated by MMPs
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Siyuan Bu , Yuchun Zhu , Chuandu Peng , Xiang Cai , Chenxi Cao , Hong Tan , Jingqiu Cheng , Jie Zhang , Jiaming Liu , Hong Li , Kunjie Wang
      Mechanical stimulation is an essential factor for organisms to develop normally. In bladder development matrix metalloproteinases (MMPs) play an important role through structure remodeling and regulating the cell proliferation. In this study, we investigated the simulated physiological stretch induced proliferation of HBSMCs; MMPs/TIMPs expression in stretch and non-stretch groups. HBSMCs were exposed to cyclic stretch with defined parameters (5%, 10% and 15% elongation). The expression of MMPs and TIMPs in each parameter and non-stretch groups was examined at the transcriptional and translational levels respectively. 5-Ethynyl-2′-deoxyuridine (EdU) assay was used to assess cell proliferation. In the presence of the broad spectrum MMPs inhibitor (Batimastat), cells proliferation, MMPs and tissue inhibitors of metalloproteinases (TIMPs) expression were assessed again. Compared with non-stretch group, HBSMCs in stretch groups showed higher proliferation. The expression of MMP-1, 2, 3, 7 was up-regulated in stretch groups, and it remained at the same high level in 10% and 15% stretch groups. TIMP-1, 2 expression only increased under 15% stretch. Stretch resulted in elevated cell proliferation was abolished by Batimastat. In conclusion, the proliferation of HBSMCs induced by stretch was resulted from the stretch-induced MMPs expression and release.


      PubDate: 2014-10-31T07:10:37Z
       
  • Polycomb chromobox (Cbx) 7 modulates activation-induced CD4+ T cell
           apoptosis
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Jian Li , Yang Li , Yinyin Cao , Meifen Yuan , Zhengfeng Gao , Xuemei Guo , Fenhua Zhu , Yunfeng Wang , Jin Xu
      CD4+ T cell polarization plays a critical role in a number of immune disorders; the pathogenesis is unclear. Chromobox homolog 7 (Cbx7) is involved in the gene transcription of several cell types. This study aims to investigate the mechanism by which Cbx7 modulates the CD4+ T cell polarization. Expression of Cbx7 was assessed by quantitative RT-PCR and Western blotting. Apoptosis of CD4+ T cell was analyzed by flow cytometry. The FasL promoter methylation was evaluated by the methylation specific PCR. The results showed that CD4+ CD25− T cells express Cbx7 that was increased significantly after activation by exposing to anti-CD3/CD28 Ab, but suppressed by exposing to specific antigens. More apoptotic cells were detected in CD4+ T cells with the Cbx7 gene knockdown. Exposure to insulin-like growth factor-1 up regulated the expression of Cbx7 in CD4+ T cells. After antigen-specific TCR activation, Cbx7-deficient CD4+ T cells expressed more FasL and showed the FasL gene promoter hyper demethylation than wild CD4+ T cells. In addition, CD4+ T cells with overexpression of Cbx7 showed lower levels of FasL gene promoter demethylation. We conclude that CD4+ T cells express Cbx7; the latter prevents FasL expression and the activation-induced CD4+ T cell apoptosis.


      PubDate: 2014-10-31T07:10:37Z
       
  • Calpains and cancer: Friends or enemies'
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Daniele Moretti , Barbara Del Bello , Giulia Allavena , Emilia Maellaro
      Calpains are a complex family of ubiquitous or tissue-specific cysteine proteases that proteolyze a variety of substrates (leading to their degradation or functional modulation) and are implicated in several pathophysiological phenomena. In tumor cell biology, calpains are implicated in a triple way: they are involved in different processes crucial for tumor progression, including cell proliferation, apoptotic cell death, survival mechanisms, migration and invasiveness; they have aberrant expression in several human cancers; a variety of anticancer drugs induce cytotoxicity through activation of calpains or the latter can influence response to therapy. This review covers established and recent literature showing these diverse aspects in tumor cells.


      PubDate: 2014-10-31T07:10:37Z
       
  • Identification and characterization of new family members in the
           tautomerase superfamily: Analysis and implications
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Jamison P. Huddleston , Elizabeth A. Burks , Christian P. Whitman
      Tautomerase superfamily members are characterized by a β–α–β building block and a catalytic amino terminal proline. 4-Oxalocrotonate tautomerase (4-OT) and malonate semialdehyde decarboxylase (MSAD) are the title enzymes of two of the five known families in the superfamily. Two recent developments in these families indicate that there might be more metabolic diversity in the tautomerase superfamily than previously thought. 4-OT homologues have been identified in three biosynthetic pathways, whereas all previously characterized 4-OTs are found in catabolic pathways. In the MSAD family, homologues have been characterized that lack decarboxylase activity, but have a modest hydratase activity using 2-oxo-3-pentynoate. This observation stands in contrast to the first characterized MSAD, which is a proficient decarboxylase and a less efficient hydratase. The hydratase activity was thought to be a vestigial and promiscuous activity. However, this recent discovery suggests that the hydratase activity might reflect a new activity in the MSAD family for an unknown substrate. These discoveries open up new avenues of research in the tautomerase superfamily.
      Graphical abstract image

      PubDate: 2014-10-31T07:10:37Z
       
  • Metabolomics in cell culture—A strategy to study crucial metabolic
           pathways in cancer development and the response to treatment
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Anna Halama
      Metabolomics is a comprehensive tool for monitoring processes within biological systems. Thus, metabolomics may be widely applied to the determination of diagnostic biomarkers for certain diseases or treatment outcomes. There is significant potential for metabolomics to be implemented in cancer research because cancer may modify metabolic pathways in the whole organism. However, not all biological questions can be answered solely by the examination of small molecule composition in biofluids; in particular, the study of cellular processes or preclinical drug testing requires ex vivo models. The major objective of this review was to summarise the current achievement in the field of metabolomics in cancer cell culture—focusing on the metabolic pathways regulated in different cancer cell lines—and progress that has been made in the area of drug screening and development by the implementation of metabolomics in cell lines.


      PubDate: 2014-10-31T07:10:37Z
       
  • Heme oxygenase-1 and anti-inflammatory M2 macrophages
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Yuji Naito , Tomohisa Takagi , Yasuki Higashimura
      Heme oxygenase-1 (HO-1) catalyzes the first and rate-limiting enzymatic step of heme degradation and produces carbon monoxide, free iron, and biliverdin. HO-1, a stress-inducible protein, is induced by various oxidative and inflammatory signals. Consequently, HO-1 expression has been regarded as an adaptive cellular response against inflammatory response and oxidative injury. Although several transcriptional factors and signaling cascades are involved in HO-1 regulation, the two main pathways of Nrf2/Bach1 system and IL-10/HO-1 axis exist in monocyte/macrophage. Macrophages are broadly divisible into two groups: pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. More recently, several novel macrophage subsets have been identified including Mhem, Mox, and M4 macrophages. Of these, M2 macrophages, Mhem, and Mox are HO-1 highly expressing macrophages. HO-1 has been recognized as having major immunomodulatory and anti-inflammatory properties, which have been demonstrated in HO-1 deficient mice and human cases of genetic HO-1 deficiency. However, the mechanism underlying the immunomodulatory actions of HO-1 remains poorly defined. This review specifically addresses macrophage polarization. The present current evidence indicates that HO-1 induction mediated by multiple pathways can drive the phenotypic shift to M2 macrophages and suggests that HO-1 induction in macrophages is a potential therapeutic approach to immunomodulation in widely diverse human diseases.


      PubDate: 2014-10-31T07:10:37Z
       
  • MiR-29a is an enhancer of mineral deposition in bone-derived systems
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): V.P. Roberto , D.M. Tiago , I.A.L. Silva , M.L. Cancela
      MicroRNAs (miRNAs) provide a mechanism for fine-tuning of intricate cellular processes through post-transcriptional regulation. Emerging evidences indicate that miRNAs play key roles in regulation of osteogenesis. The miR-29 family was previously implicated in mammalian osteoblast differentiation by targeting extracellular matrix molecules and modulating Wnt signaling. Nevertheless, the function of miR-29 in bone formation and homeostasis is not completely understood. Here, we provide novel insights into the biological effect of miR-29a overexpression in a mineralogenic cell system (ABSa15). MiR-29a gain-of-function resulted in significant increase of extracellular matrix mineralization, probably due to accelerated differentiation. We also demonstrated for the first time that miR-29a induced β-catenin protein levels, implying a stimulation of canonical Wnt signaling. Our data also suggests that SPARC is a conserved target of miR-29a, and may contribute to the phenotype observed in ABSa15 cells. Finally, we provide evidences for miR-29a conservation throughout evolution based on sequence homology, synteny analysis and expression patterns. Concluding, miR-29a is a key player in osteogenic differentiation, leading to increased mineralization in vitro, and this function seems to be conserved throughout vertebrate evolution by interaction with canonical Wnt signaling and conservation of targets.


      PubDate: 2014-10-31T07:10:37Z
       
  • A pre-steady state and steady state kinetic analysis of the N-ribosyl
           hydrolase activity of hCD157
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Frank Preugschat , Luke H. Carter , Eric E. Boros , David J.T. Porter , Eugene L. Stewart , Lisa M. Shewchuk
      hCD157 catalyzes the hydrolysis of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The release of nicotinamide or nicotinic acid from NR or NAR was confirmed by spectrophotometric, HPLC and NMR analyses. hCD157 is inactivated by a mechanism-based inhibitor, 2′-deoxy-2′-fluoro-nicotinamide arabinoside (fNR). Modification of the enzyme during the catalytic cycle by NR, NAR, or fNR increased the intrinsic protein fluorescence by approximately 50%. Pre-steady state and steady state data were used to derive a minimal kinetic scheme for the hydrolysis of NR. After initial complex formation a reversible step (360 and 30s−1) is followed by a slow irreversible step (0.1s−1) that defined the rate limiting step, or kcat . The calculated KMapp value for NR in the hydrolytic reaction is 6nM. The values of the kinetic constants suggest that one biological function of cell-surface hCD157 is to bind and slowly hydrolyze NR, possibly converting it to a ligand-activated receptor. Differences in substrate preference between hCD157 and hCD38 were rationalized through a comparison of the crystal structures of the two proteins. This comparison identified several residues in hCD157 (F108 and F173) that can potentially hinder the binding of dinucleotide substrates (NAD+).


      PubDate: 2014-10-31T07:10:37Z
       
  • Lactococcus lactis TrxD represents a subgroup of thioredoxins prevalent in
           Gram-positive bacteria containing WCXDC active site motifs
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Olof Björnberg , Petr Efler , Epie Denis Ebong , Birte Svensson , Per Hägglund
      Three protein disulfide reductases of the thioredoxin superfamily from the industrially important Gram-positive Lactococcus lactis (LlTrxA, LlTrxD and LlNrdH) are compared to the “classical” thioredoxin from Escherichia coli (EcTrx1). LlTrxA resembles EcTrx1 with a WCGPC active site motif and other key residues conserved. By contrast, LlTrxD is more distantly related and contains a WCGDC motif. Bioinformatics analysis suggests that LlTrxD represents a subgroup of thioredoxins from Gram-positive bacteria. LlNrdH is a glutaredoxin-like electron donor for ribonucleotide reductase class Ib. Based on protein–protein equilibria LlTrxA (E°′=−259mV) and LlNrdH (E°′=−238mV) show approximately 10mV higher standard state redox potentials than the corresponding E. coli homologues, while E°′ of LlTrxD is −243mV, more similar to glutaredoxin than “classical” thioredoxin. EcTrx1 and LlTrxA have high capacity to reduce insulin disulfides and their exposed active site thiol is alkylated at a similar rate at pH 7.0. LlTrxD on the other hand, is alkylated by iodoacetamide at almost 100 fold higher rate and shows no activity towards insulin disulfides. LlTrxA, LlTrxD and LlNrdH are all efficiently reduced by NADPH dependent thioredoxin reductase (TrxR) from L. lactis and good cross-reactivity towards E. coli TrxR was observed with LlTrxD as the notable exception.


      PubDate: 2014-10-31T07:10:37Z
       
  • Na,K-ATPase reconstituted in ternary liposome: The presence of cholesterol
           affects protein activity and thermal stability
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Juliana Sakamoto Yoneda , Carolina Fortes Rigos , Thaís Fernanda Aranda de Lourenço , Heitor Gobbi Sebinelli , Pietro Ciancaglini
      Differential scanning calorimetry (DSC) was applied to investigate the effect of cholesterol on the thermotropic properties of the lipid membrane (DPPC and DPPE). The thermostability and unfolding of solubilized and reconstituted Na,K-ATPase in DPPC:DPPE:cholesterol-liposomes was also studied to gain insight into the role of cholesterol in the Na,K-ATPase modulation of enzyme function and activity. The tertiary system (DPPC:DPPE:cholesterol) (molar ratio DPPC:DPPE equal 1:1) when cholesterol content was increased from 0% up to 40% results in a slight decrease in the temperature of transition and enthalpy, and an increase in width. We observed that, without heating treatment, at 37°C, the activity was higher for 20mol% cholesterol. However, thermal inactivation experiments showed that the enzyme activity loss time depends on the cholesterol membrane content. The unfolding of the enzyme incorporated to liposomes of DPPC:DPPE (1:1mol) with different cholesterol contents, ranging from 0% to 40% mol was also studied by DSC. Some differences between the thermograms indicate that the presence of lipids promotes a conformational change in protein structure and this change is enough to change the way Na,K-ATPase thermally unfolds.
      Graphical abstract image

      PubDate: 2014-10-31T07:10:37Z
       
  • Molecular network including eIF1AX, RPS7, and 14-3-3γ regulates
           protein translation and cell proliferation in bovine mammary epithelial
           cells
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Cuiping Yu , Chaochao Luo , Bo Qu , Nagam Khudhair , Xinyu Gu , Yanli Zang , Chunmei Wang , Na Zhang , Qingzhang Li , Xuejun Gao
      14-3-3γ, an isoform of the 14-3-3 protein family, was proved to be a positive regulator of mTOR pathway. Here, we analyzed the function of 14-3-3γ in protein synthesis using bovine mammary epithelial cells (BMECs). We found that 14-3-3γ interacted with eIF1AX and RPS7 by 14-3-3γ coimmunoprecipitation (CoIP) and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI-TOF/TOF) peptide mass fingerprinting analysis. These interactions of 14-3-3γ with eIF1AX and RPS7 were further confirmed by colocalization and fluorescence resonance energy transfer (FRET) analysis. We also found that methionine could promote protein synthesis and trigger the protein expression levels of 14-3-3γ, eIF1AX and RPS7. Analysis of overexpression and inhibition of 14-3-3γ confirmed that it positively affected the protein expression levels of eIF1AX, RPS7, Stat5 and mTOR pathway to promote protein synthesis and cell proliferation in BMECs. We further showed that overexpression of eIF1AX and RPS7 also triggered protein translation and cell proliferation. From these results, we conclude that molecular network including eIF1AX, RPS7, and 14-3-3γ regulates protein translation and cell proliferation in BMECs.


      PubDate: 2014-10-31T07:10:37Z
       
  • Biochemical characterization of the retaining glycosyltransferase
           glucosyl-3-phosphoglycerate synthase from Mycobacterium tuberculosis
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Garima Kumar , Siqi Guan , Patrick A. Frantom
      Glucosyl-3-phosphoglycerate synthase (GpgS) catalyzes the first step in the biosynthesis of glucosyl glycerate, the putative precursor used in building methylated polysaccharides in mycobacteria. Enzymes from Mycobacterium tuberculosis (MtGpgS) and related species have been structurally characterized and subjected to basic kinetic analyses, but more in-depth kinetic analysis is currently lacking. Dead-end inhibition studies with MtGpgS suggest an ordered kinetic mechanism with 3-phosphoglycerate (3-PGA) binding first, followed by UDP-glucose, in contrast to previous reports. At higher concentrations, 3-PGA exhibits competitive substrate inhibition vs. UDP-glucose, suggesting 3-PGA can bind to either binding site on the enzyme. Parabolic noncompetitive inhibition plots by a 3-PGA analog also support this conclusion. The effect of varying pH on the catalytic parameters indicates single ionizable residue involved catalysis (pK a =6.3) that must be deprotonated for full activity. A solvent kinetic isotope effect of 2.0±0.3 on k cat is consistent with a proton in flight during the rate-determining step. Site-directed mutagenesis studies identify several residues critical for interactions with substrates. Although the residues are conserved among other glycosyltransferase families catalyzing similar reactions, the effect of substitutions varies between families suggesting that conserved areas play different catalytic roles in each family.


      PubDate: 2014-10-31T07:10:37Z
       
  • TPPII, MYBBP1A and CDK2 form a protein–protein interaction network
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Jarmila Nahálková , Birgitta Tomkinson
      Tripeptidyl-peptidase II (TPPII) is an aminopeptidase with suggested regulatory effects on cell cycle, apoptosis and senescence. A protein–protein interaction study revealed that TPPII physically interacts with the tumor suppressor MYBBP1A and the cell cycle regulator protein CDK2. Mutual protein–protein interaction was detected between MYBBP1A and CDK2 as well. In situ Proximity Ligation Assay (PLA) using HEK293 cells overexpressing TPPII forming highly enzymatically active oligomeric complexes showed that the cytoplasmic interaction frequency of TPPII with MYBBP1A increased with the protein expression of TPPII and using serum-free cell growth conditions. A specific reversible inhibitor of TPPII, butabindide, suppressed the cytoplasmic interactions of TPPII and MYBBP1A both in control HEK293 and the cells overexpressing murine TPPII. The interaction of MYBBP1A with CDK2 was confirmed by in situ PLA in two different mammalian cell lines. Functional link between TPPII and MYBBP1A has been verified by gene expression study during anoikis, where overexpression of TPP II decreased mRNA expression level of MYBBP1A at the cell detachment conditions. All three interacting proteins TPPII, MYBBP1A and CDK2 have been previously implicated in the research for development of tumor-suppressing agents. This is the first report presenting mutual protein–protein interaction network of these proteins.


      PubDate: 2014-10-31T07:10:37Z
       
  • Characterization of the kinetics and electron paramagnetic resonance
           spectroscopic properties of Acidithiobacillus ferrooxidans sulfide:quinone
           oxidoreductase (SQR)
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Yanfei Zhang , Joel H. Weiner
      Acidithiobacillus ferrooxidans sulfide:quinone oxidoreductase (SQR) catalyzes the oxidation of sulfide to polysulfide chains or elemental sulfur coupled to quinone reduction via a non-covalent FAD cofactor. We investigated the role of the FAD using kinetics and EPR spectroscopy. The properties of the enzyme were compared with alanine and/or serine variants of conserved cysteine residues (Cys128, Cys160, Cys356) structurally close to the FAD cofactor and histidine residues (His132, His198) implicated in function. When the pre-steady state reduction of FAD was monitored, variants of Cys128 and His132 had similar rates to wild-type enzyme confirming they do not participate in the reductive half reaction whereas variants of Cys160, Cys356 and His198 had greatly reduced activity. Using steady state kinetics of Na2S-dependent decylubiquinone (DUQ) reduction we measured a k cat of 6.5s−1 and a K m (Na2S) of 3.0μM and a K m (DUQ) of 3.4μM. Variants of Cys160, Cys356 and His198 had greatly diminished DUQ reduction activity whereas variants of Cys128 and His132 were less affected. A neutral flavin semiquinone was observed in the EPR spectrum of SQR reduced with Na2S which was enhanced in the Cys160Ala variant suggesting the presence of a Cys356-Sγ-S-C4A-FAD adduct. Potentiometric titrations of the FAD semiquinone revealed an E m of −139±4mV at pH 7.0.


      PubDate: 2014-10-31T07:10:37Z
       
  • Energy landscapes reveal the myopathic effects of tropomyosin mutations
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Marek Orzechowski , Stefan Fischer , Jeffrey R. Moore , William Lehman , Gerrie P. Farman
      Striated muscle contraction is regulated by an interaction network connecting the effects of troponin, Ca2+, and myosin-heads to the azimuthal positioning of tropomyosin along thin filaments. Many missense mutations, located at the actin–tropomyosin interface, however, reset the regulatory switching mechanism either by weakening or strengthening residue-specific interactions, leading to hyper- or hypo-contractile pathologies. Here, we compute energy landscapes for the actin–tropomyosin interface and quantify contributions of single amino acid residues to actin–tropomyosin binding. The method is a useful tool to assess effects of actin and tropomyosin mutations, potentially relating initial stages of myopathy to alterations in thin filament stability and regulation. Landscapes for mutant filaments linked to hyper-contractility provide a simple picture that describes a decrease in actin–tropomyosin interaction energy. Destabilizing the blocked (relaxed)-state parallels previously noted enhanced Ca2+-sensitivity conferred by these mutants. Energy landscapes also identify post-translational modifications that can rescue regulatory imbalances. For example, cardiomyopathy-associated E62Q tropomyosin mutation weakens actin–tropomyosin interaction, but phosphorylation of neighboring S61 rescues the binding-deficit, results confirmed experimentally by in vitro motility assays. Unlike results on hyper-contractility-related mutants, landscapes for tropomyosin mutants tied to hypo-contractility do not present a straightforward picture. These mutations may affect other components of the regulatory network, e.g., troponin–tropomyosin signaling.
      Graphical abstract image Highlights

      PubDate: 2014-10-31T07:10:37Z
       
  • Prediction of the influences of missense mutations on cholesteryl ester
           transfer protein structure
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Alexander D. Dergunov
      The structure of human plasma cholesteryl ester transfer protein (CETP) was mapped in silico by a search of the structural effects of missense mutations in the CETP gene. Sixteen deleterious substitutions were chosen among 54 known missense mutations and further ranked by stability change score into six structural and ten functional mutations with large and small stability changes, respectively. A cluster of eight mutations in a central region spanning residues 184–296 with exclusively destabilizing effects was evident. Moreover, the mutations were differently distributed between ordered and highly fluctuating regions. Putative cholesterol-binding regions, mostly unique for CETP in a whole CETP-including protein family, were identified. Three of six structural mutations influence cholesteryl ester and phosphatidylcholine binding by CETP. The local partially disordered structure of some putative cholesterol-binding regions is suggested to be differently influenced by cholesterol binding. This may underlie the impairment of the local ordering effect of cholesterol by the L261R substitution. Also, cholesterol may competitively inhibit cholesteryl ester binding to the CETP molecule, with triglyceride binding being largely undisturbed. This analysis may contribute to the ongoing design and mechanistic studies of new CETP inhibitors.
      Graphical abstract image

      PubDate: 2014-10-31T07:10:37Z
       
  • SLC41A1 knockdown inhibits angiotensin II-induced cardiac fibrosis by
           preventing Mg2+ efflux and Ca2+ signaling in cardiac fibroblasts
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Na Yu , Jianmin Jiang , Yang Yu , Hong Li , Xiaoyang Huang , Yunzi Ma , Luankun Zhang , Jian Zou , Boyu Zhang , Shaorui Chen , Peiqing Liu
      Na+/Mg2+ exchanger plays an important role in cardiovascular system, but the molecular mechanisms still largely remain unknown. The Solute Carrier family 41A1 (SLC41A1), a novel Mg2+ transporter, recently was found to function as Na+/Mg2+ exchanger, which mainly regulates the intracellular Mg2+ ([Mg2+] i ) homeostasis. Our present studies were designed to investigate whether SLC41A1 impacts on the fibrogenesis of cardiac fibroblasts under Ang II stimulation. Our results showed that quinidine, a prototypical inhibitor of Na+/Mg2+ exchanger, inhibited Ang II-induced cardiac fibrosis via attenuating the overexpression of vital biomarkers of fibrosis, including connective tissue growth factor (CTGF), fibronectin (FN) and α-smooth muscle actin (α-SMA). In addition, quinidine also decreased the Ang II-mediated elevation of concentration of intracellular Ca2+ ([Ca2+] i ) and extrusion of intracellular Mg2+. Meanwhile, silencing SLC41A1 by RNA interference also impaired the elevation of [Ca2+] i , [Mg2+] i efflux and the upregulation of CTGF, FN and α-SMA provoked by Ang II. Furthermore, we found that Ang II-mediated activation of NFATc4 translocation decreased in SLC41A1-siRNA cells. These results support the notion that rapid extrusion of intracellular Mg2+ is mediated by SLC41A1 and provide the evidence that the intracellular free Ca2+ concentration is influenced by extrusion of intracellular Mg2+ which facilitates fibrosis reaction in cardiac fibroblasts.


      PubDate: 2014-10-31T07:10:37Z
       
  • Sexually dimorphic myofilament function in a mouse model of nemaline
           myopathy
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Johan Lindqvist , Edna C. Hardeman , Julien Ochala
      Nemaline myopathy, the most common congenital myopathy, is characterized by mutations in genes encoding myofilament proteins such as skeletal α-actin. These mutations are thought to ultimately lead to skeletal muscle weakness. Interestingly, some of the mutations appear to be more potent in males than in females. The underlying mechanisms remain obscure but may be related to sex-specific differences in the myofilament function of both limb and respiratory muscles. To verify this, in the present study, we used skeletal muscles (tibialis anterior and diaphragm) from a transgenic mouse model harbouring the His40Tyr amino acid substitution in skeletal α-actin. In this animal model, 60% of males die by 13weeks of age (the underlying causes of death are obscure but probably due to respiratory insufficiency) whereas females have a normal lifespan. By recording and analysing the mechanics of membrane-permeabilized myofibres, we only observed sex-related differences in the tibialis anterior muscles. Indeed, the concomitant deficits in maximal steady-state isometric force and stiffness of myofibres were less exacerbated in transgenic females than in males, potentially explaining the lower potency in limb muscles. However, the absence of sex-difference in the diaphragm muscles was rather unexpected and suggests that myofilament dysfunction does not solely underlie the sexually dimorphic phenotypes.


      PubDate: 2014-10-31T07:10:37Z
       
  • Bovine serum albumin with glycated carboxyl groups shows
           membrane-perturbing activities
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Shin-Yi Yang , Ying-Jung Chen , Pei-Hsiu Kao , Long-Sen Chang
      The aim of the present study aimed to investigate whether glycated bovine serum albumin (BSA) showed novel activities on the lipid–water interface. Mannosylated BSA (Man-BSA) was prepared by modification of the carboxyl groups with p-aminophenyl α-d-mannopyranoside. In contrast to BSA, Man-BSA notably induced membrane permeability of egg yolk phosphatidylcholine (EYPC)/egg yolk sphingomyelin (EYSM)/cholesterol (Chol) and EYPC/EYSM vesicles. Noticeably, Man-BSA induced the fusion of EYPC/EYSM/Chol vesicles, but not of EYPC/EYSM vesicles. Although BSA and Man-BSA showed similar binding affinity for lipid vesicles, the lipid-bound conformation of Man-BSA was distinct from that of BSA. Moreover, Man-BSA adopted distinct structure upon binding with the EYPC/EYSM/Chol and EYPC/EYSM vesicles. Man-BSA could induce the fusion of EYPC/EYSM/Chol vesicles with K562 and MCF-7 cells, while Man-BSA greatly induced the leakage of Chol-depleted K562 and MCF-7 cells. The modified BSA prepared by conjugating carboxyl groups with p-aminophenyl α-d-glucopyranoside also showed membrane-perturbing activities. Collectively, our data indicate that conjugation of carboxyl groups with monosaccharide generates functional BSA with membrane-perturbing activities on the lipid–water interface.


      PubDate: 2014-10-31T07:10:37Z
       
  • Nicotinamide N-methyltransferase enhances the capacity of tumorigenesis
           associated with the promotion of cell cycle progression in human
           colorectal cancer cells
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Xinyou Xie , Haitao Yu , Yanzhong Wang , Yanwen Zhou , Guiling Li , Zhi Ruan , Fengying Li , Xiuhong Wang , Huixing Liu , Jun Zhang
      Nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many drugs and xenobiotic compounds, has been found to be overexpressed in several malignancies, including colorectal cancer. However, the biological function of NNMT and the related mechanisms in colorectal cancer have not been elucidated. In the present study, we investigated the effects of NNMT on tumorigenesis by overexpressing NNMT in the human colorectal cancer cells line SW480 which lacks constitutive NNMT expression, and downregulating NNMT expression in HT-29 cells, which exhibit high endogenous expression of NNMT. We found that NNMT significantly accelerates cell proliferation, enhances colony formation in vitro and tumorigenicity in mice; it also inhibits apoptosis, promotes cell cycle progression, increases ATP and 1-methylnicotinamide level and decreases ROS level. We also showed that 1-methylnicotinamide accelerates cell growth, inhibits apoptosis, promotes cell cycle progression, attenuates ROS production and increases ATP level. Our results indicate that NNMT enhances the capacity of tumorigenesis associated with the inhibition of cell apoptosis and the promotion of cell cycle progression in human colorectal cancer cells and the 1-methylnicotinamide increased by NNMT mediates the cellular effects of NNMT in cells. NNMT may play a vital role in energy balance and ROS induction.


      PubDate: 2014-10-31T07:10:37Z
       
  • Tryptophan oxidation in proteins exposed to thiocyanate-derived oxidants
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Vincent Bonifay , Tessa J. Barrett , David I. Pattison , Michael J. Davies , Clare L. Hawkins , Michael T. Ashby
      Human defensive peroxidases, including lactoperoxidase (LPO) and myeloperoxidase (MPO), are capable of catalyzing the oxidation of halides (X−) by H2O2 to give hypohalous acids (HOX) for the purpose of cellular defense. Substrate selectivity depends upon the relative abundance of the halides, but the pseudo-halide thiocyanate (SCN−) is a major substrate, and sometimes the exclusive substrate, of all defensive peroxidases in most physiologic fluids. The resulting hypothiocyanous acid (HOSCN) has been implicated in cellular damage via thiol oxidation. While thiols are believed to be the primary target of HOSCN in vivo, Trp residues have also been implicated as targets for HOSCN. However, the mechanism involved in HOSCN-mediated Trp oxidation was not established. Trp residues in proteins appeared to be susceptible to oxidation by HOSCN, whereas free Trp and Trp residues in small peptides were found to be unreactive. We show that HOSCN-induced Trp oxidation is dependent on pH, with oxidation of free Trp, and Trp-containing peptides observed when the pH is below 2. These conditions mimic those employed previously to precipitate proteins after treatment with HOSCN, which accounts for the discrepancy in the results reported for proteins versus free Trp and small peptides. The reactant in these cases may be thiocyanogen ((SCN)2), which is produced by comproportionation of HOSCN and SCN− at low pH. Reaction of thiocyanate-derived oxidants with protein Trp residues at low pH results in the formation of a number of oxidation products, including mono- and di-oxygenated derivatives, which are also formed with other hypohalous acids. Our data suggest that significant modification of Trp by HOSCN in vivo is likely to have limited biological relevance.


      PubDate: 2014-10-31T07:10:37Z
       
  • Intracellular crowding effects on the self-association of the bacterial
           cell division protein FtsZ
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Lamis Naddaf , Abdallah Sayyed-Ahmad
      The dimerization rate of the bacterial cell division protein FtsZ is strongly affected by the intracellular crowding. Yet the complexity of the intracellular environment makes it difficult to investigate via all-atom molecular dynamics or other detailed theoretical methods. We study the crowding effect on FtsZ dimerization which is the first step of an oligomerization process that results in more elaborate supramolecular structures. In particular, we consider the effect of intracellular crowding on the reaction rates, and their dependence on the different concentrations of crowding agents. We achieved this goal by using Brownian dynamics (BD) simulation techniques and a modified post-processing approach in which we decompose the rate constant in crowded media as a product of the rate constant in the dilute solution times a factor that incorporates the crowding effect. The latter factor accounts for the diffusion reduction and crowder induced energy. In addition we include the crowding effects on water viscosity in the BD simulations of crowded media. We finally show that biomolecular crowding has a considerable effect on the FtsZ dimerization by increasing the dimerization rate constant from 2.6×107 M−1 s−1 in the absence of crowders to 1.0×108 M−1 s−1 at crowding level of 0.30.
      Graphical abstract image

      PubDate: 2014-10-31T07:10:37Z
       
  • The GSH- and GSSG-bound structures of glutaredoxin from Clostridium
           oremlandii
    • Abstract: Publication date: 15 December 2014
      Source:Archives of Biochemistry and Biophysics, Volume 564
      Author(s): Eun Hye Lee , Hwa-Young Kim , Kwang Yeon Hwang
      Glutaredoxin (Grx) is a major redox enzyme that reduces disulfide bonds using glutathione (GSH) as an electron donor. The anaerobic bacterium Clostridium oremlandii possesses a selenocysteine-containing Grx (cGrx1) and a cysteine-containing homolog (cGrx2). Here, the crystal structure of the GSSG-bound form of cGrx2 was determined for the first time at a resolution of 1.95Å. In addition, its monothiol variant cGrx2/C15S in complex with GSH was also determined at a resolution of 1.58Å. cGrx2 is a monomeric protein with an overall structure that consists of the typical thioredoxin fold composed of four α-helices and four β-strands. Two ligands, GSH and GSSG, share a conserved binding site consisting of CPYC, TVP, and CDD motifs. The cysteinyl and γ-glutamyl moieties show similar binding interactions in the two structures, whereas the glycine moiety shows different interactions. Interestingly, the structures revealed that only one GSH moiety of GSSG is sufficient for its binding to the protein. The GSSG-bound structure of cGrx2 was obtained as an oxidized form with a disulfide bond at the CPYC motif. Comparison of the GSH-binding mode in cGrx2 to other known Grxs revealed similarities as well as some diversity.


      PubDate: 2014-10-31T07:10:37Z
       
 
 
JournalTOCs
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Email: journaltocs@hw.ac.uk
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
 
About JournalTOCs
API
Help
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2014