for Journals by Title or ISSN
for Articles by Keywords
help
  Subjects -> BIOLOGY (Total: 2590 journals)
    - BIOCHEMISTRY (192 journals)
    - BIOENGINEERING (60 journals)
    - BIOLOGY (1320 journals)
    - BIOPHYSICS (42 journals)
    - BIOTECHNOLOGY (144 journals)
    - BOTANY (192 journals)
    - CYTOLOGY AND HISTOLOGY (25 journals)
    - ENTOMOLOGY (53 journals)
    - GENETICS (136 journals)
    - MICROBIOLOGY (208 journals)
    - MICROSCOPY (9 journals)
    - ORNITHOLOGY (23 journals)
    - PHYSIOLOGY (66 journals)
    - ZOOLOGY (120 journals)

BIOCHEMISTRY (192 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: 236)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 13)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 8)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 5)
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: 6)
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: 130)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 11)
Amino Acids     Hybrid Journal   (Followers: 7)
Analytical Biochemistry     Hybrid Journal   (Followers: 159)
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)
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 13)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 2)
Biochemical Engineering Journal     Hybrid Journal   (Followers: 8)
Biochemical Genetics     Hybrid Journal   (Followers: 2)
Biochemical Journal     Full-text available via subscription   (Followers: 14)
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: 163)
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: 4)
Biochemistry and Cell Biology     Full-text available via subscription   (Followers: 8)
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: 16)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 5)
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: 5)
BioInorganic Reaction Mechanisms     Full-text available via subscription   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 11)
Biomedicines     Open Access  
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)
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: 17)
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: 3)
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: 13)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 2)
DNA Barcodes     Open Access  
Doklady Biochemistry and Biophysics     Hybrid Journal   (Followers: 2)
Doklady Chemistry     Hybrid Journal  
Egyptian Journal of Biochemistry and Molecular Biology     Full-text available via subscription  

        1 2     

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  [2563 journals]   [SJR: 1.131]   [H-I: 115]
  • CD24 regulates stemness and the epithelial to mesenchymal transition
           through modulation of Notch1 mRNA stability by p38MAPK
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Juyeon Lim , Kyung-min Lee , Jaekyung Shim , Incheol Shin
      We report here that CD24 knockdown resulted in decreased expression of Notch1 in MCF-7 cells. CD24-downstream p38MAPK was shown to regulate Notch1 at the level of mRNA stability. We also found that CD24-mediated cell migration, invasion, mammosphere formation, and drug resistance was regulated by its downstream target Notch1. Together, our results indicate that CD24 may regulate the epithelial to mesenchymal transition and stemness through Notch1 signaling in breast cancer cells.


      PubDate: 2014-07-30T20:25:07Z
       
  • Atmospheric-pressure plasma jet induces DNA double-strand breaks that
           require a Rad51-mediated homologous recombination for repair in
           Saccharomyces cerevisiae
    • Abstract: Publication date: Available online 30 July 2014
      Source:Archives of Biochemistry and Biophysics
      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. 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: 2014-07-30T20:25:07Z
       
  • Hypoxic conditions differentially regulate TAZ and YAP in cancer cells
    • Abstract: Publication date: Available online 29 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-30T20:25:07Z
       
  • Dynamic profile and adipogenic role of growth differentiation factor 5
           (GDF5) in the differentiation of 3T3-L1 preadipocytes
    • Abstract: Publication date: Available online 28 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-30T20:25:07Z
       
  • 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: Available online 27 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-30T20:25:07Z
       
  • 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: Available online 19 July 2014
      Source:Archives of Biochemistry and Biophysics
      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, 1H, 13C, 15N HSQC 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: 2014-07-26T20:02:45Z
       
  • Cancer and bone: A complex complex
    • Abstract: Publication date: Available online 18 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-26T20:02:45Z
       
  • Identification of important residues of insulin-like peptide 5 and its
           receptor RXFP4 for ligand–receptor interactions
    • Abstract: Publication date: Available online 18 July 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Xin-Yi Wang , Yu-Qi Guo , Xiao-Xia Shao , Ya-Li Liu , Zeng-Guang Xu , Zhan-Yun Guo
      Insulin-like peptide 5 (INSL5) is an insulin/relaxin superfamily peptide involved in the regulation of glucose homeostasis by activating its receptor RXFP4, which can also be activated by relaxin-3 in vitro. To determine the interaction mechanism of INSL5 with its receptor RXFP4, we studied their electrostatic interactions using a charge-exchange mutagenesis approach. First, we identified three negatively charged extracellular residues (Glu100, Asp104 and Glu182) in human RXFP4 that were important for receptor activation by wild-type INSL5. Second, we demonstrated that two positively charged B-chain Arg residues (B13Arg and B23Arg) in human INSL5 were involved in receptor binding and activation. Third, we proposed probable electrostatic interactions between INSL5 and RXFP4: the B-chain central B13Arg of INSL5 interacts with both Asp104 and Glu182 of RXFP4, meanwhile the B-chain C-terminal B23Arg of INSL5 interacts with both Glu100 and Asp104 of RXFP4. The present electrostatic interactions between INSL5 and RXFP4 were similar to our previously identified interactions between relaxin-3 and RXFP4, but had subtle differences that might be caused by the different B-chain C-terminal conformations of relaxin-3 and INSL5 because a dipeptide exchange at the B-chain C-terminus significantly decreased the activity of INSL5 and relaxin-3 to receptor RXFP4.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Disrupted calcium homeostasis is involved in elevated zinc ion-induced
           photoreceptor cell death
    • Abstract: Publication date: Available online 19 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-26T20:02:45Z
       
  • G-quadruplex formation of FXYD1 pre-mRNA indicates the possibility of
           regulating expression of its protein product
    • Abstract: Publication date: Available online 19 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-26T20:02:45Z
       
  • Sex disparities in melanoma outcomes: The role of biology
    • Abstract: Publication date: Available online 21 July 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Adi Nostrati , 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: 2014-07-26T20:02:45Z
       
  • Folding energetics and oligomerization of polytopic α-helical
           transmembrane proteins
    • Abstract: Publication date: Available online 21 July 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jennifer Neumann , Noreen Klein , Daniel E. Otzen , Dirk Schneider
      While interactions of single-span transmembrane helices have been studied to a significant extent in the past years, the folding of polytopic α-helical transmembrane proteins as well as their oligomerization, are far less analyzed and understood. The goal of the few thus far performed thermodynamic studies, in which unfolding of polytopic TM proteins was described, was to achieve a mild, potentially reversible unfolding process, to finally derive thermodynamic parameters for the reverse folding pathway. In the first part of this review, we summarize the studies analyzing the thermodynamic stability and folding pathways of polytopic transmembrane proteins. Based on these studies, we deduce some common principles, guiding transmembrane protein unfolding and folding, important for the design of future folding/unfolding studies. Furthermore, the discussed observations can conceptually guide an experimental search for proper in vitro transmembrane protein refolding conditions. In many of the resolved membrane protein structures, individual monomers interact to form higher ordered oligomers. In most cases, oligomerization of those monomeric units appears to be intimately linked to the protein function, and folding of the individual protomers might even occur only after interaction. In the second part of this review, we discuss folding pathways of oligomeric α-helical transmembrane proteins as well as causes and consequences of α-helical transmembrane protein oligomerization.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Imatinib binding to human serum albumin modulates heme association and
           reactivity
    • Abstract: Publication date: Available online 21 July 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Elena Di Muzio , Fabio Polticelli , Viviana Trezza , Gabriella Fanali , Mauro Fasano , Paolo Ascenzi
      Imatinib, an inhibitor of the Bcr-Abl tyrosine kinase, is approximately 95% bound to plasma proteins, α1-acid glycoprotein (AGP) being the primary carrier. However, human serum albumin (HSA) may represent the secondary carrier of imatinib in pathological states characterized by low AGP levels, such as pancreatic cancer, hepatic cirrhosis, hepatitis, hyperthyroidism, nephrotic syndrome, malnutrition, and cachexia. Here, thermodynamics of imatinib binding to full-length HSA and its recombinant Asp1-Glu382 truncated form (containing only the FA1, FA2, FA6, and FA7 binding sites; trHSA), in the absence and presence of ferric heme (heme-Fe(III)), and the thermodynamics of heme-Fe(III) binding to HSA and trHSA, in the absence and presence of imatinib, has been investigated. Moreover, the effect of imatinib on kinetics of peroxynitrite detoxification by ferric human serum heme-albumin (HSA-heme-Fe(III)) and ferric truncated human serum heme-albumin (trHSA-heme-Fe(III)) has been explored. All data were obtained at pH 7.0, and 20.0°C and 37.0°C. Imatinib binding to the FA7 site of HSA and trHSA inhibits allosterically heme-Fe(III) association to the FA1 site and vice versa, according to linked functions. Moreover, imatinib binding to the secondary FA2 site of HSA-heme-Fe(III) inhibits allosterically peroxynitrite detoxification. Docking simulations and local structural comparison with other imatinib-binding proteins support functional data indicating the preferential binding of imatinib to the FA1 and FA7 sites of HSA, and to the FA2 and FA7 sites of HSA-heme-Fe(III). Present results highlight the allosteric coupling of the FA1, FA2, and FA7 sites of HSA, and may be relevant in modulating ligand binding and reactivity properties of HSA in vivo.


      PubDate: 2014-07-26T20:02:45Z
       
  • Low-molecular-weight thiols in plants: functional and analytical
           implications
    • Abstract: Publication date: Available online 21 July 2014
      Source:Archives of Biochemistry and Biophysics
      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,andrecently-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 decipherthe roles of thiols in plant metabolism.
      Graphical abstract image Highlights

      PubDate: 2014-07-26T20:02:45Z
       
  • The role of microRNAs and long non-coding RNAs in the pathology,
           diagnosis, and management of melanoma
    • Abstract: Publication date: Available online 24 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-26T20:02:45Z
       
  • In Saccharomyces cerevisiae fructose-1,6-bisphosphate contributes to the
           Crabtree effect through closure of the mitochondrial unspecific channel
    • Abstract: Publication date: August 2014
      Source:Archives of Biochemistry and Biophysics, Volumes 555–556
      Author(s): Mónica Rosas-Lemus , Cristina Uribe-Alvarez , Natalia Chiquete-Félix , Salvador Uribe-Carvajal
      In Saccharomyces cerevisiae addition of glucose inhibits oxygen consumption, i.e. S. cerevisiae is Crabtree-positive. During active glycolysis hexoses-phosphate accumulate, and probably interact with mitochondria. In an effort to understand the mechanism underlying the Crabtree effect, the effect of two glycolysis-derived hexoses-phosphate was tested on the S. cerevisiae mitochondrial unspecific channel ( Sc MUC). Glucose-6-phosphate (G6P) promoted partial opening of Sc MUC, which led to proton leakage and uncoupling which in turn resulted in, accelerated oxygen consumption. In contrast, fructose-1,6-bisphosphate (F1,6BP) closed Sc MUC and thus inhibited the rate of oxygen consumption. When added together, F1,6BP reverted the mild G6P-induced effects. F1,6BP is proposed to be an important modulator of Sc MUC, whose closure contributes to the “Crabtree effect”.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Inhibition of human glutathione transferases by dinitronaphthalene
           derivatives
    • Abstract: Publication date: August 2014
      Source:Archives of Biochemistry and Biophysics, Volumes 555–556
      Author(s): Hilary Groom , Moses Lee , Pravin Patil , P. David Josephy
      Glutathione transferase (GST) enzymes catalyze the conjugation of glutathione with reactive functional groups of endogenous compounds and xenobiotics, including halonitroaromatics. 1-Chloro-2,4-dinitrobenzene (CDNB) is one of the most commonly used substrates for GST activity assays. We have studied the interactions of dinitronaphthalene analogues of CDNB with recombinant human GST enzymes (Alpha, Mu, and Pi classes) expressed in Escherichia coli. Dinitronaphthalene derivatives were found to be GST inhibitors. The highest potency of inhibition was observed towards Mu-class GSTs, M1-1 and M2-2; IC50 values for 1-methoxy- and 1-ethoxy-2,4-dinitronaphthalene were in the high nanomolar to low micromolar range. Inhibition accompanies the formation, at the enzyme active site, of very stable Meisenheimer complex intermediates.


      PubDate: 2014-07-26T20:02:45Z
       
  • Matrix Gla protein and osteocalcin: from gene duplication to
           neofunctionalization
    • Abstract: Publication date: Available online 25 July 2014
      Source:Archives of Biochemistry and Biophysics
      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: 2014-07-26T20:02:45Z
       
  • Oxidation, inactivation and aggregation of protein disulfide isomerase
           promoted by the bicarbonate-dependent peroxidase activity of human
           superoxide dismutase
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Asif Iqbal , Veronica Paviani , Ana Iochabel Moretti , Francisco R.M. Laurindo , Ohara Augusto
      Protein disulfide isomerase (PDI) is a dithiol–disulfide oxidoreductase that has essential roles in redox protein folding. PDI has been associated with protective roles against protein aggregation, a hallmark of neurodegenerative diseases. Intriguingly, PDI has been detected in the protein inclusions found in the central nervous system of patients of neurodegenerative diseases. Oxidized proteins are also consistently detected in such patients, but the agents that promote these oxidations remain undefined. A potential trigger of protein oxidation is the bicarbonate-dependent peroxidase activity of the human enzyme superoxide dismutase 1 (hSOD1). Therefore, we examined the effects of this activity on PDI structure and activity. The results showed that PDI was oxidized to radicals that lead to PDI inactivation and aggregation. The aggregates are huge and apparently produced by covalent cross-links. Spin trapping experiments coupled with MS analysis indicated that at least 3 residues of PDI are oxidized to tyrosyl radicals (Y63, Y116 and Y327). Parallel experiments showed that PDI is also oxidized to radicals, inactivated and aggregated by the action of photolytically generated carbonate radical and by UV light. PDI is prone to inactivation and aggregation by one-electron oxidants and UV light probably because of its high content of aromatic amino acids.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • 20S proteasome activity is modified via S-glutathionylation based on
           intracellular redox status of the yeast Saccharomyces cerevisiae:
           Implications for the degradation of oxidized proteins
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Marilene Demasi , Adrian Hand , Erina Ohara , Cristiano L.P. Oliveira , Renata N. Bicev , Clelia A. Bertoncini , Luis E.S. Netto
      Protein S-glutathionylation is a post-translational modification that controls many cellular pathways. Recently, we demonstrated that the α5-subunit of the 20S proteasome is S-glutathionylated in yeast cells grown to the stationary phase in rich medium containing glucose, stimulating 20S core gate opening and increasing the degradation of oxidized proteins. In the present study, we evaluated the correlation between proteasomal S-glutathionylation and the intracellular redox status. The redox status was controlled by growing yeast cells in distinct carbon sources which induced respiratory (glycerol/ethanol) or fermentative (glucose) metabolism. Cells grown under glycerol/ethanol displayed higher reductive power when compared to cells grown under glucose. When purified from cells grown in glucose, 20S proteasome α5-subunit exhibited an intense anti-glutathione labeling. A higher frequency of the open catalytic chamber gate was observed in the S-glutathionylated preparations as demonstrated by transmission electron microscopy. Therefore, cells that had been grown in glucose displayed an increased ability to degrade oxidized proteins. The results of the present study suggest that 20S proteasomal S-glutathionylation is a relevant adaptive response to oxidative stress that is capable to sense the intracellular redox environment, leading to the removal of oxidized proteins via a process that is not dependent upon ubiquitylation and ATP consumption.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Oxidatively generated base damage to cellular DNA by hydroxyl radical and
           one-electron oxidants: Similarities and differences
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Jean Cadet , J. Richard Wagner
      Hydroxyl radical ( OH) and one-electron oxidants that may be endogenously formed through oxidative metabolism, phagocytosis, inflammation and pathological conditions constitute the main sources of oxidatively generated damage to cellular DNA. It is worth mentioning that exposure of cells to exogenous physical agents (UV light, high intensity UV laser, ionizing radiation) and chemicals may also induce oxidatively generated damage to DNA. Emphasis is placed in this short review article on the mechanistic aspects of OH and one-electron oxidant-mediated formation of single and more complex damage (tandem lesions, intra- and interstrand cross-links, DNA–protein cross-links) in cellular DNA arising from one radical hit. This concerns DNA modifications that have been accurately measured using suitable analytical methods such as high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Evidence is provided that OH and one-electron oxidants after generating neutral radicals and base radical cations respectively may partly induce common degradation pathways. In addition, selective oxidative reactions giving rise to specific degradation products of OH and one-electron oxidation reactions that can be used as representative biomarkers of these oxidants have been identified.


      PubDate: 2014-07-26T20:02:45Z
       
  • Identification of microRNAs involved in the modulation of pro-angiogenic
           factors in atherosclerosis by a polyphenol-rich extract from propolis
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Alejandro Cuevas , Nicolás Saavedra , Marcela F. Cavalcante , Luis A. Salazar , Dulcineia S.P. Abdalla
      New vessel formation plays a critical role in the progression and vulnerability of atherosclerotic lesions. It has been shown that polyphenols from propolis attenuate the progression of atherosclerosis and also exert inhibitory effects on angiogenic factors. However, the mechanisms underlying these effects are not completely understood. Thus, this study aimed to identify microRNAs (miRNAs) involved in the modulation of pro-angiogenic factors in the atherosclerotic plaques of LDL receptor gene knockout mice treated with a polyphenol-rich extract of Chilean propolis. The progression of the atherosclerotic lesions was significantly attenuated in treated mice compared with control mice. Using microarray analysis and a bioinformatic approach, we identified 29 differentially expressed miRNAs. Many of these miRNAs were involved in biological processes associated with angiogenesis, such as the cell cycle, cell migration, cell growth and proliferation. Among them, three miRNAs (miR-181a, miR-106a and miR-20b) were over-expressed and inversely related to the expression of Vegfa (vascular endothelial growth factor A) and Hif1a (hypoxia inducible factor 1 alpha). In addition, VEGF-A protein expression was attenuated in histological sections obtained from the aortic sinuses of treated mice. VEGFA is a key pro-angiogenic factor in atherosclerotic plaques, and Hif1a, which is expressed in the necrotic nucleus of the atheroma, is its main inducer. We found a correlation between the over-expression of miR-181a, miR-106a and miR-20b and their target genes, Hif1a and Vegfa, which is consistent with attenuation of the atherosclerotic lesion. In conclusion, our data analysis provides evidence that the anti-angiogenic effects of polyphenols from Chilean propolis can be modulated by miRNAs, in particular miR-181a, miR-106a and miR-20b.


      PubDate: 2014-07-26T20:02:45Z
       
  • Luteolin modulates expression of drug-metabolizing enzymes through the AhR
           and Nrf2 pathways in hepatic cells
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Tianshun Zhang , Yuki Kimura , Songyan Jiang , Kiyonari Harada , Yoko Yamashita , Hitoshi Ashida
      Drugs, xenobiotics including environmental pollutants, and certain food components modulate expression of drug-metabolizing enzymes. An aryl hydrocarbon receptor (AhR) possesses possible expression of phase I and phase II enzymes directly by binding of its ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and indirectly by regulating expression of nuclear factor-erythroid-2-related factor 2 (Nrf2). Previous our result demonstrated that luteolin, a natural flavonoid existing in vegetables and herbs, competed the binding of TCDD to AhR. In the present study, we investigated the effect of luteolin on the expression of drug-metabolizing enzymes through the AhR and Nrf2 pathways. Luteolin inhibited TCDD-induced protein expression of phase I enzyme cytochrome P450 1A1 (CYP1A1), phase II enzymes NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutathione-S-transferase P1 (GSTP1) in HepG2, Hepa1c1c7 and RL-34 cells in a dose-dependent manner. Luteolin suppressed TCDD- and tert-butylhydroquinone-induced Nrf2 protein by decreasing its stability in HepG2 cells. In tert-butylhydroquinone treated cells, luteolin dose-dependently inhibited NQO1, GSTP1 and aldo–keto reductases (AKRs). Of these, protein expression of CYP1A1 and GSTP1 was mainly dominated by the AhR pathway, while that of NQO1 and AKRs was by the Nrf2 pathway. In conclusion, luteolin inhibits expression of phase I and phase II drug-metabolizing enzymes by modulating the AhR and Nrf2 pathways.


      PubDate: 2014-07-26T20:02:45Z
       
  • Antioxidants and Redox Processes in Health – Bilateral Meeting
           Brazil-Japan
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Sayuri Miyamoto , Junji Terao



      PubDate: 2014-07-26T20:02:45Z
       
  • Dose-dependent functionality and toxicity of green tea polyphenols in
           experimental rodents
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Akira Murakami
      A large number of physiologically functional foods are comprised of plant polyphenols. Their antioxidative activities have been intensively studied for a long period and proposed to be one of the major mechanisms of action accounting for their health promotional and disease preventive effects. Green tea polyphenols (GTPs) are considered to possess marked anti-oxidative properties and versatile beneficial functions, including anti-inflammation and cancer prevention. On the other hand, some investigators, including us, have uncovered their toxicity at high doses presumably due to pro-oxidative properties. For instance, both experimental animal studies and epidemiological surveys have demonstrated that GTPs may cause hepatotoxicity. We also recently showed that diets containing high doses (0.5-1%) of a GTP deteriorated dextran sodium sulfate (DSS)-induced intestinal inflammation and carcinogenesis. In addition, colitis mode mice fed a 1% GTP exhibited symptoms of nephrotoxicity, as indicated by marked elevation of serum creatinine level. This diet also increased thiobarbituric acid-reactive substances, a reliable marker of oxidative damage, in both kidneys and livers even in normal mice, while the expression levels of antioxidant enzymes and heat shock proteins (HSPs) were diminished in colitis and normal mice. Intriguingly, GTPs at 0.01% and 0.1% showed hepato-protective activities, i.e., they significantly suppressed DSS-increased serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, those diets remarkably restored DSS-down-regulated expressions of heme oxygenase-1 and HSP70 in livers and kidneys. Taken together, while low and medium doses of GTPs are beneficial in colitis model mice, unwanted side-effects occasionally emerge with high doses. This dose-dependent functionality and toxicity of GTPs are in accordance with the concept of hormesis, in which mild, but not severe, stress activates defense systems for adaptation and survival.
      Graphical abstract image Highlights

      PubDate: 2014-07-26T20:02:45Z
       
  • Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of
           MDA-MB-231 human breast cancer cells by blocking β2-adrenergic
           signaling
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Shunsuke Yamazaki , Noriyuki Miyoshi , Kyuichi Kawabata , Michiko Yasuda , Kayoko Shimoi
      Endogenous catecholamines such as adrenaline (A) and noradrenaline (NA) are released from the adrenal gland and sympathetic nervous system during exposure to stress. The adrenergic system plays a central role in stress signaling, and excessive stress was found to be associated with increased production of reactive oxygen species (ROS). Overproduction of ROS induces oxidative damage in tissues and causes the development of diseases such as cancer. In this study, we investigated the effects of quercetin-3-O-glucuronide (Q3G), a circulating metabolite of quercetin, which is a type of natural flavonoid, on the catecholamine-induced β2-adrenergic receptor (β2-AR)-mediated response in MDA-MB-231 human breast cancer cells expressing β2-AR. Treatment with A or NA at concentrations above 1μM generated significant levels of ROS, and NA treatment induced the gene expression of heme oxygenase-1 (HMOX1), and matrix metalloproteinase-2 (MMP-2) and -9 (MMP9). Inhibitors of p38 MAP kinase (SB203580), cAMP-dependent protein kinase (PKA) (H-89), activator protein-1 (AP-1) transcription factor (SR11302), and NF-κB and AP-1 (Tanshinone IIA) decreased MMP2 and MMP9 gene expression. NA also enhanced cAMP induction, RAS activation and phosphorylation of ERK1/2. These results suggested that the cAMP-PKA, MAPK, and ROS-NF-κB pathways are involved in β2-AR signaling. Treatment with 0.1μM Q3G suppressed ROS generation, cAMP and RAS activation, phosphorylation of ERK1/2 and the expression of HMOX1, MMP2, and MMP9 genes. Furthermore, Q3G (0.1μM) suppressed invasion of MDA-MB-231 breast cancer cells and MMP-9 induction, and inhibited the binding of [3H]-NA to β2-AR. These results suggest that Q3G may function to suppress invasion of breast cancer cells by controlling β2-adrenergic signaling, and may be a dietary chemopreventive factor for stress-related breast cancer.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • NMR study of the Z-DNA binding mode and B–Z transition activity of
           the Zα domain of human ADAR1 when perturbed by mutation on the
           α3 helix and β-hairpin
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Minjee Jeong , Ae-Ree Lee , Hee-Eun Kim , Yong-Geun Choi , Byong-Seok Choi , Joon-Hwa Lee
      The Zα domains of human ADAR1 (ZαADAR1) bind to Z-DNA via interaction mediated by the α3-core and β-hairpin. Five residues in the α3 helix and four residues in the β-hairpin play important roles in Zα function, forming direct or water-mediated hydrogen bonds with DNA backbone phosphates or interacting hydrophobically with DNA bases. To understand the roles of these residues during B–Z transition of duplex DNA, we performed NMR experiments on complexes of various ZαADAR1 mutants with a 6-bp DNA duplex at various protein-to-DNA molar ratios. Our study suggests that single mutations at residues K169, N173, or Y177 cause unusual conformational changes in the hydrophobic faces of helices α1, α2, and α3, which dramatically decrease the Z-DNA binding affinity. 1D imino proton spectra and chemical shift perturbation showed that single mutations at residues K170, R174, T191, P192, P193, or W195 slightly affected the Z-DNA binding affinity. A hydrogen exchange study proved that the K170A- and R174A-ZαADAR1 proteins could efficiently change B-DNA to left-handed Z-DNA via an active B–Z transition pathway, whereas the G2·C5 base pair was significantly destabilized compared to wild-type ZαADAR1.


      PubDate: 2014-07-26T20:02:45Z
       
  • NMR spectroscopy reveals a preferred conformation with a defined
           hydrophobic cluster for polyglutamine binding peptide 1
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Francisco Ramos-Martín , Rubén Hervás , Mariano Carrión-Vázquez , Douglas V. Laurents
      Several important human inherited neurodegenerative diseases are caused by “polyQ expansions”, which are aberrant long repeats of glutamine residues in proteins. PolyQ binding peptide 1 (QBP1), whose minimal active core sequence is Trp-Lys-Trp-Trp-Pro-Gly-Ile-Phe, binds to expanded polyQs and blocks their β-structure transition, aggregation and in vivo neurodegeneration. Whereas QBP1 is a widely used, commercially available product, its structure is unknown. Here, we have characterized the conformations of QBP1 and a scrambled peptide (Trp-Pro-Ile-Trp-Lys-Gly-Trp-Phe) in aqueous solution by CD, fluorescence and NMR spectroscopies. A CD maximum at 227nm suggests the presence of rigid Trp side chains in QBP1. Based on 41 NOE-derived distance constraints, the 3D structure of QBP1 was determined. The side chains of Trp 4 and Ile 7, and to a lesser extent, those of Lys 2, Trp 3 and Phe 8, form a small hydrophobic cluster. Pro 5 and Gly 6 adopt a type II tight turn and Lys 2’s ζ-NH3 + is positioned to form a favorable cation–π interaction with Trp 4’s indole ring. In contrast, the scrambled QBP1 peptide, which lacks inhibitory activity, does not adopt a preferred structure. These results provide a basis for future structure-based design approaches to further optimize QBP1 for therapy.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Agaricus meleagris pyranose dehydrogenase: Influence of covalent FAD
           linkage on catalysis and stability
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Iris Krondorfer , Dagmar Brugger , Regina Paukner , Stefan Scheiblbrandner , Katharina F. Pirker , Stefan Hofbauer , Paul G. Furtmüller , Christian Obinger , Dietmar Haltrich , Clemens K. Peterbauer
      Pyranose dehydrogenase (PDH) is a monomeric flavoprotein belonging to the glucose–methanol–choline (GMC) family of oxidoreductases. It catalyzes the oxidation of free, non-phosphorylated sugars to the corresponding keto sugars. The enzyme harbors an FAD cofactor that is covalently attached to histidine 103 via an 8α-N(3) histidyl linkage. Our previous work showed that variant H103Y was still able to bind FAD (non-covalently) and perform catalysis but steady-state kinetic parameters for several substrates were negatively affected. In order to investigate the impact of the covalent FAD attachment in Agaricus meleagris PDH in more detail, pre-steady-state kinetics, reduction potential and stability of the variant H103Y in comparison to the wild-type enzyme were probed. Stopped-flow analysis revealed that the mutation slowed down the reductive half-reaction by around three orders of magnitude whereas the oxidative half-reaction was affected only to a minor degree. This was reflected by a decrease in the standard reduction potential of variant H103Y compared to the wild-type protein. The existence of an anionic semiquinone radical in the resting state of both the wild-type and variant H103Y was demonstrated using electron paramagnetic resonance (EPR) spectroscopy and suggested a higher mobility of the cofactor in the variant H103Y. Unfolding studies showed significant negative effects of the disruption of the covalent bond on thermal and conformational stability. The results are discussed with respect to the role of covalently bound FAD in catalysis and stability.


      PubDate: 2014-07-26T20:02:45Z
       
  • Shifting redox states of the iron center partitions CDO between crosslink
           formation or cysteine oxidation
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Catherine W. Njeri , Holly R. Ellis
      Cysteine dioxygenase (CDO) is a mononuclear iron-dependent enzyme that catalyzes the oxidation of l-cysteine to l-cysteine sulfinic acid. The mammalian CDO enzymes contain a thioether crosslink between Cys93 and Tyr157, and purified recombinant CDO exists as a mixture of the crosslinked and non crosslinked isoforms. The current study presents a method of expressing homogenously non crosslinked CDO using a cell permeative metal chelator in order to provide a comprehensive investigation of the non crosslinked and crosslinked isoforms. Electron paramagnetic resonance analysis of purified non crosslinked CDO revealed that the iron was in the EPR silent Fe(II) form. Activity of non crosslinked CDO monitoring dioxygen utilization showed a distinct lag phase, which correlated with crosslink formation. Generation of homogenously crosslinked CDO resulted in an ∼5-fold higher k cat/K m value compared to the enzyme with a heterogenous mixture of crosslinked and non crosslinked CDO isoforms. EPR analysis of homogenously crosslinked CDO revealed that this isoform exists in the Fe(III) form. These studies present a new perspective on the redox properties of the active site iron and demonstrate that a redox switch commits CDO towards either formation of the Cys93–Tyr157 crosslink or oxidation of the cysteine substrate.


      PubDate: 2014-07-26T20:02:45Z
       
  • AMPK inhibits cardiac hypertrophy by promoting autophagy via mTORC1
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Yanh Li , Cong Chen , Fengj Yao , Qiao Su , Dan Liu , Ruic Xue , Gang Dai , Rong Fang , Juny Zeng , Yil Chen , Huil Huang , Yued Ma , Wenw Li , Lil Zhang , Chen Liu , Yug Dong
      AMPK, a serine/threonine protein kinase, has proven to be an important positive regulator of autophagy, which is a key factor in the regulation of cardiac hypertrophy. Thus, we explored whether AMPK could inhibit cardiac hypertrophy by regulating autophagy. In pressure overload induced cardiac hypertrophy, decreased autophagy was detected. Administration of AMPK activators (AICAR and metformin) significantly blocked hypertrophy, accompanied by enhanced autophagy level in the hearts. Furthermore, AMPK activation resulted in enhanced autophagosome formation and unimpaired lysosomal function. In vitro studies demonstrated adenoviral overexpression of constitutively activated AMPK increased autophagy and blunted PE-induced cardiomyocyte hypertrophy. Additionally, we found AICAR reduced the phosphorylation of the mTORC1 downstream effectors 4EBP1 and p70S6K, but AKT, which is a downstream signal of mTORC2, was not affected. Furthermore, activation by AMPK failed to lead to an additive effect on autophagy induced by the mTORC1 inhibitor rapamycin, indicating AMPK activates autophagy through the inhibition of mTORC1 but not of mTORC2. This study proved that AMPK can inhibit cardiac hypertrophy by stimulating autophagy through mTORC1 signaling.


      PubDate: 2014-07-26T20:02:45Z
       
  • Carbenoxolone induces permeability transition pore opening in rat
           mitochondria via the translocator protein TSPO and connexin43
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Tamara Azarashvili , Yulia Baburina , Dmitry Grachev , Olga Krestinina , Vassilios Papadopoulos , John J. Lemasters , Irina Odinokova , Georg Reiser
      Ca2+-induced permeability transition pore (mPTP) opening in isolated rat brain mitochondria is promoted through targeting of connexin43. After a threshold Ca2+ load, mitochondrial membrane potential drops and efflux of accumulated Ca2+ from the mitochondrial matrix occurs, indicating the mPTP opening. Specific antibodies were used to assess the role of the translocator protein (18kDa; TSPO) and connexin43 in swelling of isolated rat liver and brain mitochondria induced by carbenoxolone and the endogenous TSPO ligand protoporphyrin IX. Mitochondrial membrane potential, Ca2+ transport and oxygen consumption were determined using selective electrodes. All the parameters were detected simultaneously in a chamber with the selective electrodes. The phosphorylation state of mitochondrial protein targets was assessed. We report that Ca2+-induced mitochondrial swelling was strengthened in the presence of both carbenoxolone and protoporphyrin IX. The carbenoxolone- and protoporphyrin IX-accelerated mPTP induction in brain mitochondria was completely prevented by antibodies specific for the mitochondrial translocator protein (TSPO). The anti-TSPO antibodies were more effective than anti-сonnexin43 antibodies. Moreover, carbenoxolone-stimulated phosphorylation of mitochondrial proteins was inhibited by anti-TSPO antibodies. Taken together, the data suggests that, in addition to acting via connexion43, carbenoxolone may exert its effect on mPTP via mitochondrial outer membrane TSPO.


      PubDate: 2014-07-26T20:02:45Z
       
  • Insulin-like modulation of Akt/FoxO signaling by copper ions is
           independent of insulin receptor
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Ingrit Hamann , Kerstin Petroll , Larson Grimm , Andrea Hartwig , Lars-Oliver Klotz
      Copper ions are known to induce insulin-like effects in various cell lines, stimulating the phosphoinositide 3′-kinase (PI3K)/Akt signaling cascade and leading to the phosphorylation of downstream targets, including FoxO transcription factors. The aim of this work was to study the role of insulin- and IGF1-receptors (IR and IGF1R) in insulin-like signaling induced by copper in HepG2 human hepatoma cells. Cells were exposed to Cu(II) at various concentrations for up to 60min. While Akt and FoxO1a/FoxO3a were strongly phosphorylated in copper- and insulin-treated cells at all time points studied, only faint tyrosine phosphorylation of IR/IGF1R was detected in cells exposed to Cu(II) by either immunoprecipitation/immunoblot or by immunoblotting using phospho-specific antibodies, whereas insulin triggered strong phosphorylation at these sites. Pharmacological inhibition of IR/IGF1R modestly attenuated Cu-induced Akt and FoxO phosphorylation, whereas no attenuation of Cu-induced Akt activation was achieved by siRNA-mediated IR depletion. Cu(II)-induced FoxO1a nuclear exclusion was only slightly impaired by pharmacological inhibition of IR/IGF1R, whereas insulin-induced effects were blunted. In contrast, genistein, a broad-spectrum tyrosine kinase inhibitor, at concentrations not affecting IR/IGF1R, attenuated Cu(II)-induced Akt phosphorylation, pointing to the requirement of tyrosine kinases other than IR/IGF1R for Cu(II)-induced signaling.


      PubDate: 2014-07-26T20:02:45Z
       
  • ATM–p53 pathway causes G2/M arrest, but represses apoptosis in
           pseudolaric acid B-treated HeLa cells
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Guodong Yao , Min Qi , Xiaoling Ji , Simiao Fan , Lei Xu , Toshihiko Hayashi , Shin-ichi Tashiro , Satoshi Onodera , Takashi Ikejima
      Pseudolaric acid B (PAB) is a diterpene acid, isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae). Previous studies demonstrated that PAB induced G2/M arrest and apoptosis in several cancer cell lines, but the relationship between G2/M arrest and apoptosis is still unclear. We examined the relevant signaling pathways for human cervical carcinoma HeLa cells treated with 1μM PAB. Intriguingly, we found that activation of ATM–p53 signaling pathway by the treatment with 1μM PAB played a protective role for the subsequent apoptosis. Although the treatment with 1μM PAB up-regulated the expression of cyclin B1 and p-Histone 3 (mitotic markers) at 12h, the expression decreased at 24 and 36h along with the up-down expression of mitotic markers. The expressions of p-ATM and p-p53 that were involved in G2/M arrest increased at 12h after treatment with PAB. However, a prolonged treatment with PAB (longer than 24h) caused cell apoptosis. When the cells were arrested in G1 or S phase by the treatment with serum starvation, cytosine β-d-arabinofuranoside (Ara-C) or hydroxyurea (Hu), the apoptotic ratio induced by PAB decreased.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth
           factor receptor-mediated signaling pathway in bradykinin-stimulated
           angiogenesis
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Miriam S. Moraes , Paulo E. Costa , Wagner L. Batista , Taysa Paschoalin , Marli F. Curcio , Roberta E. Borges , Murched O. Taha , Fábio V. Fonseca , Arnold Stern , Hugo P. Monteiro
      Nitric oxide (NO) is involved in angiogenesis and stimulates the EGF-R signaling pathway. Stimulation of different endothelial cell lines with bradykinin (BK) activates the endothelial NO synthase (eNOS) and promotes EGF-R tyrosine phosphorylation. Increase in NO production correlated with enhanced phosphorylation of tyrosine residues and S-nitrosylation of the EGF-R. NO-mediated stimulatory effects on tyrosine phosphorylation of the EGF-R, where cGMP independent. Inhibition of soluble guanylyl cyclase followed by BK stimulation of human umbilical vein endothelial cells (HUVECs) did not change tyrosine phosphorylation levels of EGF-R. BK-stimulation of HUVEC promoted S-nitrosylation of the phosphatase SHP-1 and of p21Ras. Phosphorylation and activation of the ERK1/2 MAP kinases mediated by BK was dependent on the activation of the B2 receptor, of the EGF-R, and of p21 Ras. Inhibition of BK-stimulated S-nitrosylation prevented the activation of the ERK1/2 MAP kinases. Furthermore, activated ERK1/2 MAP kinases inhibited internalization of EGF-R by phosphorylating specific Thr residues of its cytoplasmic domain. BK-induced proliferation of endothelial cells was partially inhibited by the NOS inhibitor (L-NAME) and by the MEK inhibitor (PD98059). BK stimulated the expression of vascular endothelial growth factor (VEGF). VEGF expression was dependent on the activation of the EGF-R, the B2 receptor, p21Ras, and on NO generation. A Matrigel®-based in vitro assay for angiogenesis showed that BK induced the formation of capillary-like structures in HUVEC, but not in those cells expressing a mutant of the EGF-R lacking tyrosine kinase activity. Additionally, pre-treatment of BK-stimulated HUVEC with L-NAME, PD98059, and with SU5416, a specific inhibitor of VEGFR resulted in inhibition of in vitro angiogenesis. Our findings indicate that BK-mediated angiogenesis in endothelial cells involves the induction of the expression of VEGF associated with the activation of the NO/EGF-R/p21Ras/ERK1/2 MAP kinases signaling pathway.


      PubDate: 2014-07-26T20:02:45Z
       
  • 14-3-3ζ regulates nuclear trafficking of protein phosphatase 1α
           (PP1α) in HEK-293 cells
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Myrka Jérôme , Hemant K. Paudel
      Protein phosphatase 1 (PP1) is one of the major Ser/Thr phosphatases in mammalian cells. There are four isoforms of PP1 namely, PP1α, PP1β/δ, PP1γ1 and PP1γ2. PP1γ and PP1β translocate to the nucleus by binding to a co-transporter that contains a nuclear localization signal. The mechanism by which PP1α shuttles between the nucleus and the cytosol is not known. In this study, we found that PP1α co-immunoprecipitates with 14-3-3ζ from HEK-293 cell lysates. By co-immunoprecipitation and GST pull-down assay, we determined that 14-3-3ζ binds to both PP1α (WT) and PP1α (T320A), and that phosphorylation of PP1α is not required for binding. Using PP1α deletion mutants, we located the 14-3-3ζ binding region within PP1α residues 159–279. An in vitro assay showed that 14-3-3ζ does not affect PP1α activity. When HEK-293 cells expressing PP1α and 14-3-3ζ were subjected to subcellular fractionation, the ratio of cytosolic vs. nuclear PP1α was significantly higher in cells expressing PP1α and 14-3-3ζ than those expressing PP1α alone. In cells expressing a dominant negative 14-3-3ζ (K49E), PP1α accumulated in the nucleus. Our results show that 14-3-3ζ binds to PP1α and causes its retention in the cytosol which suggests that 14-3-3ζ regulates nuclear trafficking of PP1α in mammalian cells.


      PubDate: 2014-07-26T20:02:45Z
       
  • Mechanisms of axon regeneration and its inhibition: Roles of sulfated
           glycans
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Kenji Kadomatsu , Kazuma Sakamoto
      Axons in the peripheral nervous system can regenerate after injury, whereas axons in the central nervous system (CNS) do not readily regenerate. Intrinsic regenerating capacity and emerging inhibitors could explain these contrasting phenotypes. Among the inhibitors, sulfated sugar chains including chondroitin sulfate and keratan sulfate have recently attracted attention, since these sugar chains strongly inhibit axon regeneration and also induce dystrophic endball formation, a hallmark of injured axons in the adult mammalian CNS. In addition, chondroitin sulfate is a negative regulator of synaptic plasticity. To overcome the inability of CNS axons to regenerate, a comprehensive understanding of both the positive and negative regulations of axon regeneration is required. These may include signaling waves from the injury site to the nucleus, intracellular signals for growth cone formation and axon regeneration, intracellular signals for the inhibition of axon regeneration, and extracellular inhibitory signals and their receptors. This review addresses these issues, with a focus on the roles of chondroitin sulfate and keratan sulfate.


      PubDate: 2014-07-26T20:02:45Z
       
  • The Great Beauty of the osteoclast
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      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: 2014-07-26T20:02:45Z
       
  • Expression and induction of small heat shock proteins in rat heart under
           chronic hyperglycemic conditions
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): V. Sudhakar Reddy , Ch. Uday Kumar , G. Raghu , G. Bhanuprakash Reddy
      The induction of small heat shock proteins (sHsp) is observed under various stress conditions to protect the cells and organisms from adverse events including diabetes. Diabetic cardiomyopathy is a common complication of diabetes. Therefore, in this study, we investigated the expression of sHsp under chronic hyperglycemic conditions in rat heart. Hyperglycemia was induced in WNIN rats by intraperitoneal injection of streptozotocin and maintained for a period of 12weeks. Expression of sHsp, phosphorylation and translocation of phosphoforms of Hsp27 and αB-crystallin (αBC) from cytosolic fraction to cytoskeletal fraction was analyzed. While the expression of MKBP, HspB3, αBC was found to be increased in diabetic heart, expression of Hsp20 was decreased. Chronic hyperglycemia further induced phosphorylation of αBC at S59, S45, Hsp27 at S82, p38MAPK and p44/42MAPK. However, pS59-αBC and pS82-Hsp27 were translocated from detergent-soluble to detergent-insoluble fraction under hyperglycemic conditions. Furthermore, the interaction of pS82-Hsp27 and pS59-αBC with desmin was increased under hyperglycemia. However, the interaction of αBC and pS59-αBC with Bax was impaired by chronic hyperglycemia. These results suggest up regulation of sHsp (MKBP, HspB3 and αBC), phosphorylation and translocation of Hsp27 and αBC to striated sarcomeres and impaired interaction of αBC and pS59-αBC with Bax under chronic hyperglycemia.


      PubDate: 2014-07-26T20:02:45Z
       
  • Neurogenins in brain development and disease: An overview
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Liqun Yuan , Bassem A. Hassan
      The production of neurons, astrocytes and oligodendrocytes is regulated by a group of transcription factors, which determine cell fates and specify subtype identities in the nervous system. Here we focus on profiling the distinct roles of Neurogenin (Ngn or Neurog) family members during the neuronal development. Ngn proteins are tightly regulated to be expressed at defined times and positions of different progenitor cell pools. In addition to their well-elucidated proneural function, Ngn proteins play various critical roles to specify or maintain cell fate and regulate neurite outgrowth and targeting in the central nervous system. Finally, Ngns have been associated with neuronal disorders. Therefore understanding the function and regulation of Ngns will not only improve the understanding of the molecular mechanism underlying the development of nervous system, but may also provide insight into neuronal disease.


      PubDate: 2014-07-26T20:02:45Z
       
  • Role of the disaggregase ClpB in processing of proteins aggregated as
           inclusion bodies
    • Abstract: Publication date: Available online 2 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kamila Zblewska , Joanna Krajewska , Michal Zolkiewski , Sabina Kędzierska-Mieszkowska
      Overproduction of heterologous proteins in bacterial systems often results in the formation of insoluble inclusion bodies (IBs), which is a major impediment in biochemical research and biotechnology. In principle, the activity of molecular chaperones could be employed to gain control over the IB formation and to improve the recombinant protein yields, but the potential of each of the major bacterial chaperones (DnaK/J, GroEL/ES, and ClpB) to process IBs has not been fully established yet. We investigated the formation of inclusion bodies (IBs) of two aggregation-prone proteins, VP1LAC and VP1GFP, overproduced in E scherichia coli in the presence and absence of the chaperone ClpB. We found that both ClpB isoforms, ClpB95 and ClpB80 accumulated in E. coli cells during the production of IBs. The amount of IB proteins increased in the absence of ClpB. ClpB supported the resolubilization and reactivation of the aggregated VP1LAC and VP1GFP in E. coli cells. The IB disaggregation was optimal in the presence of both ClpB95 and ClpB80. Our results indicate an essential role of ClpB in controlling protein aggregation and inclusion body formation in bacteria.


      PubDate: 2014-06-07T15:27:45Z
       
  • Activated protease receptor-2 induces GATA6 expression to promote survival
           in irradiated colon cancer cells
    • Abstract: Publication date: Available online 1 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Wen-song Cai , Fei Shen , Jiang-lin Li , Zhe Feng , Ying-cheng Wang , Huan-qing Xiao , Bo Xu
      Background and aims The resistance to irradiation is common and a great drawback in the treatment of cancer with radiotherapy; the underlying mechanism is unclear. GATA binding protein 6 (GATA6) is associated with the pathogenesis of cancer. This study aims to investigate the role of GATA6 on compromising irradiation effect on HT55 and HT29 cells, 2 colorectal cancer cell lines. Methods Human colon cancer cell lines, HT55 and HT29 cells, were treated with irradiation in the culture. Apoptosis of HT55 and HT29 cells was determined by flow cytometry. The expression of PAR2 and GATA6 in HT55 and HT29 cells was analyzed by real time RT-PCR and Western blotting. The gene silence and gene over expression were employed to observe the effect of GATA6 on p53 expression in HT55 and HT29 cells. Results The results showed that HT55 and HT29 cells expressed protease-activated receptor-2 (PAR2). Irradiation induced 38.6% HT55 cell and 33.8% HT29 cell apoptosis, which reduced to 4.2% and 5.6%, respectively after activation of PAR2. Exposure to irradiation increased the expression of GATA6; the latter played a critical role in suppression of p53 expression in HT55 and HT29 cells. Inhibition of GATA6 significantly increased the effect of irradiation on HT55 and HT29 cells. Conclusions Activation of PAR2 compromises the effect of irradiation on inducing colorectal cancer cell apoptosis, which can be prevented by inhibition of GATA6 expression.


      PubDate: 2014-06-07T15:27:45Z
       
  • Effects of the melanin precursor 5,6-dihydroxy-indole-2-carboxylic acid
           (DHICA) on DNA damage and repair in the presence of reactive oxygen
           species
    • Abstract: Publication date: Available online 1 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Maria Carolina Pellosi , Andréia Akemi Suzukawa , Alexsandra Cristina Scalfo , Paolo Di Mascio , Carolina Parga Martins Pereira , Nadja Cristhina de Souza Pinto , Daniela de Luna Martins , Glaucia Regina Martinez
      Eumelanin is a heterogeneous polymer composed of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI). Studies have shown that DHICA promotes single strand breaks in plasmid DNA exposed to ultraviolet B radiation (UVB, 313nm) and in DNA from human keratinocytes exposed to ultraviolet A radiation (UVA, 340–400nm). Singlet molecular oxygen (1O2) is the main reactive species formed by UVA radiation on the skin. In this context, we now report that DHICA can cause single strand breaks in plasmid DNA even in the absence of light radiation. Interestingly, when DHICA was pre-oxidized by 1O2, it lost this harmful capacity. It was also found that DHICA could interact with DNA, disturbing Fpg activity and decreasing its recognition of lesions by ∼50%. Additionally, the free nucleoside deoxyguanosine (dGuo) was used to evaluate whether DHICA would interfere with the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and spiroiminodihydantoin (dSp) by 1O2 or with the formation of 8-oxodGuo by hydroxyl radical ( OH). We observed that when dGuo was oxidized by 1O2 in the presence of DHICA, 8-oxodGuo formation was increased. However, when dGuo was oxidized by OH in the presence of DHICA, 8-oxodGuo levels were lower than in the absence of the precursor. Overall, our data reveal an important role for this eumelanin precursor in both the promotion and the protection of DNA damage and imply that it can impair DNA repair.


      PubDate: 2014-06-07T15:27:45Z
       
  • Specific localization of quercetin-3-O-glucuronide in human brain
    • Abstract: Publication date: Available online 1 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Akari Ishisaka , Rie Mukai , Junji Terao , Noriyuki Shibata , Yoshichika Kawai
      In recent years, many papers have suggested that dietary flavonoids may exert beneficial effects in the brain tissue for the protection of neurons against oxidative stress and inflammation. However, the bioavailability of flavonoids across the blood–brain barrier and the localization in the brain remain controversial. Thus, we examined the localization of quercetin-3-O-glucuronide (Q3GA), a major phase-II metabolite of quercetin, in the human brain tissues with or without cerebral infarction by immunohistochemical staining using anti-Q3GA antibody. A significant immunoreactivity was observed in the epithelial cells of the choroid plexus, which constitute the structural basis of the blood–cerebrospinal fluid (CSF) barrier, and in the foamy macrophages of recent infarcts. The cellular accumulation of Q3GA was also reproduced in vitro in macrophage-like RAW264, microglial MG6, and brain capillary endothelial RBEC1. It is of interest that a common feature of these cell lines is the deconjugation of Q3GA, resulting in the cellular accumulation of non-conjugated quercetin and the methylated forms. We then examined the anti-inflammatory activity of Q3GA and the deconjugated forms in the lipopolysaccharide-stimulated macrophage cells and revealed that the deconjugated forms (quercetin and a methylated form isorhamnetin), but not Q3GA itself, exhibited inhibitory effects on the inflammatory responses through attenuation of the c-Jun N-terminal kinase pathway. These results suggested that a quercetin glucuronide can pass through the blood–brain barrier, perhaps the CSF barrier, accumulate in specific types of cells, such as macrophages, and act as anti-inflammatory agents in the brain through deconjugation into the bioactive non-conjugated forms.


      PubDate: 2014-06-07T15:27:45Z
       
  • Different involvement of extracellular calcium in two modes of cell death
           induced by nanosecond pulsed electric fields
    • Abstract: Publication date: Available online 1 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Keiko Morotomi-Yano , Hidenori Akiyama , Ken-ichi Yano
      Exposure of cultured cells to nanosecond pulsed electric fields (nsPEFs) induces various cellular responses, including the influx of extracellular Ca2+ and cell death. Recently, nsPEFs have been regarded as a novel means of cancer therapy, but their molecular mechanism of action remains to be fully elucidated. Here, we demonstrate the involvement of extracellular Ca2+ in nsPEF-induced cell death. Extracellular Ca2+ was essential for necrosis and consequent poly(ADP-ribose) (PAR) formation in HeLa S3 cells. Treatment with a Ca2+ ionophore enhanced necrosis as well as PAR formation in nsPEF-exposed HeLa S3 cells. In the absence of extracellular Ca2+, HeLa S3 cells were less susceptible to nsPEFs and exhibited apoptotic proteolysis of caspase 3 and PARP-1. HeLa S3 cells retained the ability to undergo apoptosis even after nsPEF exposure but instead underwent necrosis, suggesting that necrosis is the preferential mode of cell death. In K562 and HEK293 cells, exposure to nsPEFs resulted in the formation of necrosis-associated PAR, whereas Jurkat cells exclusively underwent apoptosis independently of extracellular Ca2+. These observations demonstrate that the mode of cell death induced by nsPEFs is cell-type dependent and that extracellular Ca2+ is a critical factor for nsPEF-induced necrosis.


      PubDate: 2014-06-07T15:27:45Z
       
  • Ammonia-induced energy disorders interfere with bilirubin metabolism in
           hepatocytes
    • Abstract: Publication date: Available online 27 May 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Qiongye Wang , Yanfang Wang , Zujiang Yu , Duolu Li , Bin jia[a] Jiangjing Li , Kelei Guan , Yubing Zhou , Yanling Chen , Quancheng Kan
      Hyperammonemia and jaundice are the most common clinical symptoms of hepatic failure. Decreasing the level of ammonia in the blood is often accompanied by a reduction in bilirubin in patients with hepatic failure. Previous studies have shown that hyperammonemia can cause bilirubin metabolism disorders, however it is unclear exactly how hyperammonemia interferes with bilirubin metabolism in hepatocytes. The purpose of the current study was to determine the mechanism or mechanisms by which hyperammonemia interferes with bilirubin metabolism in hepatocytes. Cell viability and apoptosis were analyzed in primary hepatocytes that had been exposed to ammonium chloride. Mitochondrial morphology and permeability were observed and analyzed, intermediates of the tricarboxylic acid (TCA)1 cycle were determined and changes in the expression of enzymes related to bilirubin metabolism were analyzed after ammonia exposure. Hyperammonemia inhibited cell growth, induced apoptosis, damaged the mitochondria and hindered the TCA cycle in hepatocytes. This led to a reduction in energy synthesis, eventually affecting the expression of enzymes related to bilirubin metabolism, which then caused further problems with bilirubin metabolism. These effects were significant, but could be reversed with the addition of adenosine triphosphate (ATP). This study demonstrates that ammonia can cause problems with bilirubin metabolism by interfering with energy synthesis.


      PubDate: 2014-06-01T14:28:35Z
       
  • Mechanisms of reduced flavin transfer in the two-component
           flavin-dependent monooxygenases
    • Abstract: Publication date: Available online 20 May 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jeerus Sucharitakul , Ruchanok Tinikul , Pimchai Chaiyen
      Two-component flavin-dependent enzymes are abundant in nature and are involved in a wide variety of biological reactions. These enzymes consist of a reductase which generates a reduced flavin and a monooxygenase that utilizes the reduced flavin as a substrate for monooxygenation. As reduced flavin is unstable and can be oxidized by oxygen, these enzymes must have a means to efficiently coordinate the transfer of the reduced flavin such that auto-oxidation can be minimized. Various types of experiments and methodologies have been used to probe the mode of reduced flavin transfer. Results from many systems have indicated that the transfer can be achieved by free diffusion and that the presence of one component has no influence on the kinetics of the other component. Contradicting results indicating that the transfer of the reduced flavin may be achieved via protein–protein mediation also exist. Regardless of the mode of reduced flavin transfer, these enzymes have a means to control their overall kinetics such that the reaction rate is slow when the demand for oxygenation is not high.


      PubDate: 2014-05-25T16:15:16Z
       
  • Metabolomics-based search for therapeutic agents for non-alcoholic
           steatohepatitis
    • Abstract: Publication date: Available online 22 May 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Terashima Yoshihiko , Shin Nishiumi , Akihiro Minami , Yuuki Kawano , Namiko Hoshi , Takeshi Azuma , Masaru Yoshida
      Background Non-alcoholic fatty liver disease (NAFLD) is the commonest form of chronic liver disease in developed countries. Non-alcoholic steatohepatitis (NASH), which represents advanced stage NAFLD, is increasingly being recognized as a major cause of liver-related morbidity and mortality. However, no effective drugs against NASH have yet been developed. Therefore, we searched for candidate therapeutic agents based on the changes in levels of hepatic metabolites via gas chromatography mass spectrometry (GC/MS)-based metabolome analysis of livers from methionine-choline deficient (MCD) diet-fed mice, a mouse model of NASH. Methods The metabolites were extracted from the livers of the MCD diet-fed mice and then analyzed using GC/MS. Subsequently, the MCD diet-fed mice were supplemented with hypotaurine, and the therapeutic effects of hypotaurine against steatohepatitis were evaluated. Results Ninety-nine metabolites were detected in the livers of the MCD diet-induced steatohepatitis model mice. Among these metabolites, hypotaurine exhibited the greatest decrease in its concentration in the mice. Supplementation with 2 mmol/kgBW hypotaurine attenuated liver injuries and fat accumulation caused by the MCD diet-induced steatohepatitis. Furthermore, 10 mmol/kgBW hypotaurine supplementation ameliorated fibrosis and oxidative stress induced by the MCD diet. Conclusions The present metabolome analysis-based study demonstrated that hypotaurine is a novel candidate therapeutic agent for NASH.


      PubDate: 2014-05-25T16:15:16Z
       
  • Kinetic investigation of the rate-limiting step of manganese- and
           iron-lipoxygenases
    • Abstract: Publication date: Available online 21 May 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Anneli Wennman , Saeid Karkehabadi , Ernst H. Oliw
      Lipoxygenases (LOX) oxidize polyunsaturated fatty acids to hydroperoxides, which are generated by proton coupled electron transfer to the metal center with FeIIIOH- or MnIIIOH-. Hydrogen abstraction by FeIIIOH- of soybean LOX-1 (sLOX-1) is associated with a large deuterium kinetic isotope effect (D-KIE). Our goal was to compare the D-KIE and other kinetic parameters at different temperatures of sLOX-1 with 13R-LOX with catalytic manganese (13R-MnLOX). The reaction rate and the D-KIE of sLOX-1 with unlabeled and [11-2H2]18:2n-6 were almost temperature independent with an apparent D-KIE of ∼56 at 30˚C, which is in agreement with previous studies. In contrast, the reaction rate of 13R-MnLOX increased 7-fold with temperature (8 to 50˚C), and the apparent D-KIE decreased linearly from ∼38 at 8˚C to ∼20 at 50˚C. The kinetic lag phase of 13R-MnLOX was consistently extended at low temperatures. The Phe337Ile mutant of 13R-MnLOX, which catalyzes antarafacial hydrogen abstraction and oxygenation in analogy with sLOX-1, retained the large D-KIE and its temperature-dependent reaction rate. The kinetic differences between13R-MnLOX and sLOX-1 may be due to protein dynamics, hydrogen donor-acceptor distances, and to the metal ligands, which may not equalize the 0.7 V-gap between the redox potentials of the free metals.


      PubDate: 2014-05-25T16:15:16Z
       
  • Modulation of tumor cell stiffnessand migration by type IV collagenthrough
           direct activation of integrin signaling pathway
    • Abstract: Publication date: Available online 10 May 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sheng-Yi Chen , Jo-Shi Lin , Bei-Chang Yang
      Excessive collagen deposition plays a critical rolein tumor progression and metastasis. To understand how type IV collagen affects mechanical stiffness andmigration,low-collagen-IV-expressing transfectantsof B16F10, U118MG, and Huh7(denoted shCol cells) were established by the lentiviral-mediated delivery of small interfering RNA againsttype IV-α1 collagen (Col4A1). Although having similar growth rates, shCol cells showed a flatter morphology compared to that of thecorresponding controls. Notably, knocking down theCol4A1geneconferred the cells withhigher levels of elasticityand lower motility.Exposure to blocking antibodies against human β1integrinor α2β1integrinor the pharmacologicalinhibition ofSrc and ERK activity by PP1 and U0126, respectively, effectively reducedcell motility and raisedcell stiffness. Reduced Src and ERK activitiesin shCol cells indicate theinvolvement of a collagen IV/integrin signaling pathway. The forced expression ofβ1integrinsignificantly stimulated Src and ERK phosphorylation, reduced cell stiffness, and acceleratedcell motility. In an experimental metastasis assay using C57BL/6 mice, B16F10 shColcells formed significantly fewer and smaller lung nodules,confirming the contribution of collagen to metastasis.In summary, theintegrin signaling pathway activated in a tumor environment with collagendeposition is responsible for low cell elasticity and high metastatic ability.


      PubDate: 2014-05-14T12:56:24Z
       
 
 
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