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  Subjects -> BIOLOGY (Total: 2698 journals)
    - BIOCHEMISTRY (206 journals)
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    - BIOLOGY (1342 journals)
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BIOCHEMISTRY (206 journals)                  1 2 3     

AAPS PharmSciTech     Hybrid Journal   (Followers: 7)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Chemical Biology     Full-text available via subscription   (Followers: 342)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 13)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 9)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 6)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 8)
Advances in Biological Chemistry     Open Access   (Followers: 5)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 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: 201)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 11)
American Journal of Polymer Science     Open Access   (Followers: 17)
Amino Acids     Hybrid Journal   (Followers: 7)
Analytical Biochemistry     Hybrid Journal   (Followers: 231)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 29)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 10)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 17)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 7)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 4)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 9)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (Followers: 1)
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Asian Journal of Biomedical and Pharmaceutical Sciences     Open Access   (Followers: 1)
Avicenna Journal of Medical Biochemistry     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 3)
Biocatalysis     Open Access  
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 15)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 3)
Biochemical Compounds     Open Access  
Biochemical Engineering Journal     Hybrid Journal   (Followers: 9)
Biochemical Genetics     Hybrid Journal   (Followers: 2)
Biochemical Journal     Full-text available via subscription   (Followers: 16)
Biochemical Pharmacology     Hybrid Journal   (Followers: 6)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 3)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 253)
Biochemistry (Moscow)     Hybrid Journal   (Followers: 3)
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology     Hybrid Journal   (Followers: 4)
Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry     Hybrid Journal   (Followers: 3)
Biochemistry and Cell Biology     Full-text available via subscription   (Followers: 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: 18)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 6)
Biochimie     Hybrid Journal   (Followers: 4)
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 14)
BioDrugs     Full-text available via subscription   (Followers: 7)
Bioelectrochemistry     Hybrid Journal   (Followers: 3)
Biofuels     Hybrid Journal   (Followers: 8)
Biogeochemistry     Hybrid Journal   (Followers: 7)
BioInorganic Reaction Mechanisms     Full-text available via subscription   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 11)
Biomaterials Research     Open Access  
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Full-text available via subscription   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 6)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 18)
BMC Biochemistry     Open Access   (Followers: 8)
BMC Chemical Biology     Open Access   (Followers: 4)
Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca : Food Science and Technology     Open Access  
Carbohydrate Polymers     Hybrid Journal   (Followers: 9)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 6)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 3)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
Central European Journal of Chemistry     Hybrid Journal   (Followers: 5)
ChemBioChem     Hybrid Journal   (Followers: 2)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 23)
Chemical Engineering Journal     Hybrid Journal   (Followers: 20)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Full-text available via subscription   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 2)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 17)
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: 6)
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: 5)
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)

        1 2 3     

Journal Cover Archives of Biochemistry and Biophysics     [SJR: 1.131]   [H-I: 115]
   [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  [2585 journals]
  • Theoretical studies of the hydrolysis of antibiotics catalyzed by a
           Metallo-β-lactamase
    • Abstract: Publication date: Available online 23 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): C. Meliá , S. Ferrer , V. Moliner , J. Bertrán
      In this paper, hybrid QM/MM molecular dynamics (MD) simulations have been performed to explore the mechanisms of hydrolysis of two antibiotics, Imipenen (IMI), an antibiotic belonging to the subgroup of carbapenems, and the Cefotaxime (CEF), a third-generation cephalosporin antibiotic, in the active site of a mono-nuclear β-lactamase, CphA from Aeromonas hydrophila. Significant different transition state structures are obtained for the hydrolysis of both antibiotics: while the TS of the CEF is a ionic species with negative charge on nitrogen, the IMI TS presents a tetrahedral-like character with negative charge on oxygen atom of the carbonyl group of the lactam ring. Thus, dramatic conformational changes can take place in the cavity of CphA to accommodate different substrates, which would be the origin of its substrate promiscuity. Since CphA shows only activity against carbapenem antibiotic, this study sheds some light into the origin of the selectivity of the different MbL and, as a consequence, into the discovery of specific and potent MβL inhibitors against a broad spectrum of bacterial pathogens. We have finally probed that a re-parametrization of semiempirical methods should be done to properly describe the behaviour the metal cation in active site, Zn2+, when used in QM/MM calculations.
      Graphical abstract image Highlights

      PubDate: 2015-01-23T17:35:42Z
       
  • How our bodies fight amyloidosis: effects of physiological factors on
           pathogenic aggregation of amyloidogenic proteins
    • Abstract: Publication date: Available online 20 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Lianqi Huang , Xinran Liu , Biao Cheng , Kun Huang
      The process of protein aggregation from soluble amyloidogenic proteins to insoluble amyloid fibrils plays significant roles in the onset of over 30 human amyloidogenic diseases, such as Prion disease, Alzheimer’s disease and type 2 Diabetes Mellitus. Amyloid deposits are commonly found in patients suffered from amyloidosis; however, such deposits are rarely seen in healthy individuals, which may be largely attributed to the self-regulation in vivo. A vast number of physiological factors have been demonstrated to directly affect the process of amyloid formation in vivo. In this review, physiological factors that influence amyloidosis, including biological factors (chaperones, natural antibodies, enzymes, lipids and saccharides) and physicochemical factors (metal ions, pH environment, crowding and pressure, etc), together with the mechanisms underlying these proteostasis effects, are summarized.


      PubDate: 2015-01-23T17:35:42Z
       
  • Analysis of genetic polymorphism and biochemical characterization of a
           functionally decreased variant in prostacyclin synthase gene (CYP8A1) in
           humans
    • Abstract: Publication date: Available online 23 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Sun-Ah Cho , Katie Jo Rohn-Glowacki , Yazun B. Jarrar , Myeongjin Yi , Woo-Young Kim , Jae-Gook Shin , Su-Jun Lee
      Prostacyclin synthase (CYP8A1) is an enzyme responsible for the biosynthesis of prostacyclin (PGI2) which inhibits platelet activation and exhibits anti-inflammatory effect. The objectives of this study were to identify CYP8A1 genetic variants and characterize functional consequences of CYP8A1 variants. In total, 27 variants including four previously unidentified single-nucleotide polymorphisms (SNPs) were identified by direct DNA sequencing in Koreans (n = 48). Among them, CYP8A1 A447T and E314Stop were newly assigned as CYP8A1∗5 and CYP8A1∗6 by the Human Cytochrome P450 Allele Nomenclature Committee, respectively. CYP8A1∗5 was found in the heme binding area in three individuals as a heterozygous mutation. To investigate the functional change of CYP8A1∗5, CYP8A1∗5 and wild-type CYP8A1 protein were overexpressed in an Escherichia coli expression system and purified. Metabolism of PGH2 by the CYP8A1∗5 protein exhibited significantly decreased activity, resulting in a 45% decrease in Vmax and a 1.8-fold decrease in intrinsic clearance compared to the wild-type. Based on the predicted crystal structure of CYP8A1∗5 using the Molecular Operating Environment platform, the distance from CYP8A1 Cys441 to the heme was altered with a significantly changed binding free energy for the mutant protein. Further studies would be needed to determine the effect of CYP8A1∗5 on PGI2 levels in humans.
      Graphical abstract image

      PubDate: 2015-01-23T17:35:42Z
       
  • A comprehensive review on the colorless carotenoids phytoene and
           phytofluene
    • Abstract: Publication date: Available online 20 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Antonio J. Meléndez-Martínez , Paula Mapelli-Brahm , Ana Benítez-González , Carla M. Stinco
      Carotenoids and their derivatives are versatile isoprenoids involved in many varied actions, hence their importance in the agri-food industry, nutrition, health and other fields. All carotenoids are derived from the colorless carotenes phytoene and phytofluene, which are oddities among carotenoids due to their distinct chemical structure. They occur together with lycopene in tomato and other lycopene-containing foods. Furthermore, they are also present in frequently consumed products like oranges and carrots, among others. The intake of phytoene plus phytofluene has been shown to be higher than that of lycopene and other carotenoids in Luxembourg. This is likely to be common in other countries. However, they are not included in food carotenoid databases, hence they have not been linked to health benefits in epidemiological studies. Interestingly, there are evidences in vitro, animal models and humans indicating that they may provide health benefits. In this sense, the study of these colorless carotenes in the context of food science, nutrition and health should be further encouraged. In this work, we review much of the existing knowledge concerning their chemical characteristics, physico-chemical properties, analysis, distribution in foods, bioavailability and likely biological activities.


      PubDate: 2015-01-23T17:35:42Z
       
  • Imaging and characterizing cells using tomography
    • Abstract: Publication date: Available online 17 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Myan Do , Samuel A. Isaacson , Gerry McDermott , Mark A. Le Gros , Carolyn A. Larabell
      We can learn much about cell function by imaging and quantifying sub-cellular structures, especially if this is done non-destructively without altering said structures. Soft x-ray tomography (SXT) is a high-resolution imaging technique for visualizing cells and their interior structure in 3D. A tomogram of the cell, reconstructed from a series of 2D projection images, can be easily segmented and analyzed. SXT has a very high specimen throughput compared to other high-resolution structure imaging modalities; for example, tomographic data for reconstructing an entire eukaryotic cell is acquired in a matter of minutes. SXT visualizes cells without the need for chemical fixation, dehydration, or staining of the specimen. As a result, the SXT reconstructions are close representations of cells in their native state. SXT is applicable to most cell types. The deep penetration of soft x-rays allows cells, even mammalian cells, to be imaged without being sectioned. Image contrast in SXT is generated by the differential attenuation soft x-ray illumination as it passes through the specimen. Accordingly, each voxel in the tomographic reconstruction has a measured linear absorption coefficient (LAC) value. LAC values are quantitative and give rise to each sub-cellular component having a characteristic LAC profile, allowing organelles to be identified and segmented from the milieu of other cell contents. In this chapter, we describe the fundamentals of SXT imaging and how this technique can answer real world questions in the study of the nucleus. We also describe the development of correlative methods for the localization of specific molecules in a SXT reconstruction. The combination of fluorescence and SXT data acquired from the same specimen produces composite 3D images, rich with detailed information on the inner workings of cells.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • Elastic proteins in the flight muscle of Manduca sexta
    • Abstract: Publication date: Available online 17 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Chen-Ching Yuan , Weikang Ma , Peter Schemmel , Yu-Shu Cheng , Jiangmin Liu , George Tsaprailis , Samuel Feldman , Agnes Ayme Southgate , Thomas C. Irving
      The flight muscles (DLM1) of the Hawkmoth, Manduca sexta are synchronous, requiring a neural spike for each contraction. Stress/strain curves of skinned DLM1 showed hysteresis indicating the presence of titin-like elastic proteins. Projectin and kettin are titin-like proteins previously identified in Lethocerus and Drosophila flight muscles. Analysis of Manduca muscles with 1% SDS-agarose gels and western blots showed two bands near 1MDa that cross-reacted with antibodies to Drosophila projectin. Antibodies to Drosophila kettin cross-reacted to bands at ∼500 and ∼700kDa, but also to bands at ∼1.6 and ∼2.1MDa, that had not been previously observed in insect flight muscles. Mass spectrometry identified the 2.1MDa protein as a product of the Sallimus (sls) gene. Analysis of the gene sequence showed that all 4 putative Sallimus and kettin isoforms could be explained as products of alternative splicing of the single sls gene. Both projectin and Sallimus isoforms were expressed to higher levels in ventrally located DLM1 subunits, primarily responsible for active work production, as compared to dorsally located subunits, which may act as damped springs. The different expression levels of the 2 projectin isoforms and 4 Sallimus/kettin isoforms may be adaptations to the specific requirements of individual muscle subunits.


      PubDate: 2015-01-19T17:11:57Z
       
  • Actions of β-Apo-Carotenoids in Differentiating Cells: Differential
           Effects in P19 Cells and 3T3-L1 Adipocytes
    • Abstract: Publication date: Available online 17 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Cynthia X. Wang , Hongfeng Jiang , Jason J. Yuen , Seung-Ah Lee , Sureshbabu Narayanasamy , Robert W. Curley Jr. , Earl H. Harrison , William S. Blaner
      β-Apo-carotenoids, including β-apo-13-carotenone and β-apo-14’-carotenal, are potent retinoic acid receptor (RAR) antagonists in transactivation assays. We asked how these influence RAR-dependent processes in living cells. Initially, we explored the effects of β-apo-13-carotenone and β-apo-14’-carotenal on P19 cells, a mouse embryonal carcinoma cell line that differentiates into neurons when treated with all-trans-retinoic acid. Treatment of P19 cells with either compound failed to block all-trans-retinoic acid induced differentiation. Liquid chromatography tandem mass spectrometry studies, however, established that neither of these β-apo-carotenoids accumulates in P19 cells. All-trans-retinoic acid accumulated to high levels in P19 cells. This suggests that the uptake and metabolism of β-apo-carotenoids by some cells does not involve the same processes used for retinoids and that these may be cell type specific. We also investigated the effects of two β-apo-carotenoids on 3T3-L1 adipocyte marker gene expression during adipocyte differentiation. Treatment of 3T3-L1 adipocytes with either β-apo-13-carotenone or β-apo-10’-carotenoic acid, which lacks RAR antagonist activity, stimulated adipocyte marker gene expression. Neither blocked the inhibitory effects of a relatively large dose of exogenous all-trans-retinoic acid on adipocyte differentiation. Our data suggest that in addition to acting as transcriptional antagonists, some β-apo-carotenoids act through other mechanisms to influence 3T3-L1 adipocyte differentiation.


      PubDate: 2015-01-19T17:11:57Z
       
  • Tissue- and sex-specific effects of β-carotene 15,15’ oxygenase
           (BCO1) on retinoid and lipid metabolism in adult and developing mice
    • Abstract: Publication date: Available online 17 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Youn-Kyung Kim , Michael V. Zuccaro , Brianna K. Costabile , Rebeka Rodas , Loredana Quadro
      In mammals, β-carotene-15,15’-oxygenase (BCO1) is the main enzyme that cleaves β-carotene, the most abundant vitamin A precursor, to generate retinoids (vitamin A derivatives), both in adult and developing tissues. We previously reported that, in addition to this function, BCO1 can also influence the synthesis of retinyl esters, the storage form of retinoids, in the mouse embryo at mid-gestation. Indeed, lack of embryonic BCO1 impaired both lecithin-dependent and acyl CoA-dependent retinol esterification, mediated by lecithin:retinol acyltransferase (LRAT) and acyl CoA:retinol acyltransferase (ARAT), respectively. Furthermore, embryonic BCO1 also influenced the ester pools of cholesterol and diacylglycerol. In this report, we gained novel insights into this alternative function of BCO1 by investigating whether BCO1 influenced embryonic retinoid and lipid metabolism in a tissue-dependent manner. To this end, livers and brains from wild-type and BCO1-/- embryos at mid-gestation were analyzed for retinoid and lipid content, as well as gene expression levels. We also asked whether or not the role of BCO1 as a regulator of lecithin- and acyl CoA-dependent retinol esterification was exclusively restricted to the developing tissues. Thus, a survey of retinol and retinyl ester levels in adult tissues of wild-type, BCO1-/-, LRAT-/- and LRAT-/-BCO1-/- mice was performed. We showed that the absence of BCO1 affects embryonic retinoid and lipid homeostasis in a tissue-specific manner and that retinyl ester formation is also influenced by BCO1 in a few adult tissues (pancreas, lung, heart and adipose) in a sex- dependent manner.


      PubDate: 2015-01-19T17:11:57Z
       
  • Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker
           rat model
    • Abstract: Publication date: Available online 17 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kazim Sahin , Brian Cross , Nurhan Sahin , Karina Ciccone , Shadeah Suleiman , Adeboye Osunkoya , Viraj Master , Wayne Harris , Bradley Carthon , Ramzi Mohammad , Birdal Bilir , Karin Wertz , Carlos S. Moreno , Cheryl L. Walker , Omer Kucuk
      Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80–85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n =90) were assigned in equal numbers to receive 0, 100 or 200mg/kg of lycopene as part of their daily diet. After 18months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin–eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (P <0.12). However, mean numbers of renal carcinomas were statistically significantly decreased in the lycopene-treated rats (P <0.008) when compared to untreated controls. In the lycopene group, tumor numbers decreased (P <0.002) and the numbers tended to decrease linearly (P <0.003) as supplemental lycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98mm) than rats fed lycopene supplement groups (12.90mm and 11.07mm) (P <0.05). Moreover tumor length decreased (P <0.02) and tumor length tended to decrease linearly (P <0.03) as supplemental lycopene increased from 0 to 200mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC.


      PubDate: 2015-01-19T17:11:57Z
       
  • Structure and heme-binding properties of HemQ (chlorite dismutase-like
           protein) from Listeria monocytogenes
    • Abstract: Publication date: Available online 17 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Stefan Hofbauer , Andreas Hagmüller , Irene Schaffner , Georg Mlynek , Michael Krutzler , Gerhard Stadlmayr , Katharina F. Pirker , Christian Obinger , Holger Daims , Kristina Djinović-Carugo , Paul G. Furtmüller
      Chlorite dismutase-like proteins are structurally closely related to functional chlorite dismutases, which are heme b-dependent oxidoreductases capable of reducing chlorite to chloride with simultaneous production of dioxygen. Chlorite dismutase-like proteins are incapable of performing this reaction and their biological role is still under discussion. Recently, members of this large protein family were shown to be involved in heme biosynthesis in Gram-positive bacteria, and thus the protein was renamed HemQ in these organisms. In the present work the structural and heme binding properties of the chlorite dismutase-like protein from the Gram-positive pathogen Listeria monocytogenes (LmCld) were analysed in order to evaluate its potential role as a regulatory heme sensing protein. The homopentameric crystal structure (2.0 Å) shows high similarity to chlorite-degrading chlorite dismutases with an important difference in the structure of the putative substrate and heme entrance channel. In solution LmCld is a stable hexamer able to bind the low-spin ligand cyanide. Heme binding is reversible with K D-values determined to be 7.2 μM (circular dichroism spectroscopy) and 16.8 μM (isothermal titration calorimetry) at pH 7.0. Both acidic and alkaline conditions promote heme release. Presented biochemical and structural data reveal that the chlorite dismutase-like protein from Listeria monocytogenes could act as a potential regulatory heme sensing and storage protein within heme biosynthesis.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • New labeled derivatives of the neuroprotective peptide colivelin:
           Synthesis, characterization, and first in vitro and in vivo applications
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Myrta Kostomoiri , Christos Zikos , Dimitra Benaki , Charalampos Triantis , Marina Sagnou , Maria Paravatou-Petsotas , Amalia Papadaki , Haralabia Boleti , Minas Papadopoulos , Ioannis Pirmettis , Maria Pelecanou , Evangelia Livaniou
      Colivelin (CL), first reported in 2005, is the most potent member of the humanin family of neuroprotective peptides with in vitro and in vivo rescuing action against insults associated with Alzheimer’s disease (AD). The objective of the present work is the design, synthesis and characterization of specific CL derivatives that can be used as molecular probes in the investigation of the unknown mechanism of CL action. Within this framework, three CL derivatives bearing suitable tags, i.e., the fluorescent moiety FITC, the streptavidin-counterpart biotinyl-group, and the 99mTc-radiometal chelating unit dimethylGly-Ser-Cys, were developed and subsequently applied in biological evaluation experiments. Specifically, the FITC-labeled derivative of CL was used in confocal microscopy, where specific binding at the periphery of F11 cells was observed; the biotin-labeled derivative of CL was used in an in-house developed ELISA-type assay, where specific and concentration-dependent binding with the β-amyloid peptide of AD was shown; finally, the 99mTc-radiolabeled derivative of CL was used in in vivo biodistribution studies in healthy Swiss Albino mice, where 0.58% of the radioactivity administered was measured in the mouse brain 2min after injection. The above first successful applications of the CL probes demonstrate their potential to contribute in the field of neuroprotective peptides.


      PubDate: 2015-01-19T17:11:57Z
       
  • UV light selectively inhibits spinal cord inflammation and demyelination
           in experimental autoimmune encephalomyelitis
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Yanping Wang , Steven J. Marling , Emily F. Beaver , Kyle S. Severson , Hector F. Deluca
      Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The incidence of MS is inversely related to sun light exposure or ultraviolet radiation (UVR). UVR was found to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS, independent of vitamin D production. The mechanism of this suppression remains to be elucidated. To this end, several elements of an immune response in the spinal cord, spleen and skin during development of EAE were studied. As expected, UVR (10kJ/m2) inhibits inflammation and demyelination of the spinal cord. Most significant, UVR dramatically reduced spinal cord chemokine CCL5 mRNA and protein levels. UVR also suppressed IL-10 in skin and spleen but not the spinal cord. As expected from the UVR action on skin, macrophage population and IFN-γ levels are increased in that organ. UVR had no effect on lymphocyte proliferation and IFN-γ in spleen. From these measurements, we suggest that UVR suppression of EAE prevents the migration of inflammatory cells into the CNS by a focal inhibition of chemokine CCL-5 in the CNS and a systemic elevation of immunosuppressive IL-10.


      PubDate: 2015-01-19T17:11:57Z
       
  • Endurance training prevents TWEAK but not myostatin-mediated cardiac
           remodelling in cancer cachexia
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Ana Isabel Padrão , Daniel Moreira-Gonçalves , Paula A. Oliveira , Catarina Teixeira , Ana I. Faustino-Rocha , Luísa Helguero , Rui Vitorino , Lúcio Lara Santos , Francisco Amado , José Alberto Duarte , Rita Ferreira
      Strategies to prevent tumour burden-induced cardiac remodelling that might progress to heart failure are necessary to improve patients’ health outcomes and tolerability to cancer therapies. Exercise has been suggested as a measure to prevent cardiac damage; however, its effectiveness on regulating cardiac remodelling secondary to cancer was never addressed. Using an animal model of mammary tumorigenesis, we studied the impact of 35weeks of endurance training on heart, focusing on the signalling pathways modulated by pro-inflammatory and wasting cytokines. The cardiac fibrosis and myofiber disorganization induced by tumour burden was paralleled by the increase of myostatin and TWEAK with the activation of signalling pathways involving Smad-3, NF-κB, TRAF-6 and atrogin-1. The activation of Akt/mTOR was observed in heart from rats with tumours, for which contributed the extracellular matrix. Endurance training prevented the increase of serum and cardiac TWEAK promoted by cancer, as well as the activation of NF-κB, TRAF6, atrogin-1 and p70S6K in heart. Data highlight the impact of exercise in the modulation of signalling pathways activated by wasting cytokines and the resulting outcomes on heart adaptation. Future studies focused on the cellular pathways underlying cardiac remodelling will assist in the development of exercise programs targeting cancer-related cardiac alterations.


      PubDate: 2015-01-19T17:11:57Z
       
  • Sulfated and sulfonated polymers are able to solubilize efficiently the
           protein aggregates of different nature
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Pavel I. Semenyuk , Evgeniya V. Moiseeva , Yulia Yu. Stroylova , Marina Lotti , Vladimir A. Izumrudov , Vladimir I. Muronetz
      The search for new ways to suppress unwanted protein aggregation represents an important problem in modern biochemistry, bioengineering, and even medicine. Recently we succeeded in preventing the aggregation using synthetic polyelectrolytes. The present work describes a new approach to solubilizing pre-formed protein aggregates with sulfated or sulfonated polymers (polysulfoanions). For the first time it was shown that polysulfoanions are capable of solubilizing amorphous and amyloid protein inclusion bodies as well as thermal aggregates. Treatment of prion protein inclusion bodies with sulfonated polymers was shown to cause significant decrease in amyloid structure content, whereas in case of thermal aggregates of glyceraldehyde-3-phosphate dehydrogenase the observed solubilization was accompanied by a partial recovery of enzymatic activity. The suggested approach could be relevant in the task of extracting recombinant proteins from inclusion bodies and also useful in the development of amyloid disease therapy.
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      PubDate: 2015-01-19T17:11:57Z
       
  • Control of the ribulose 1,5-bisphosphate carboxylase/oxygenase activity by
           the chloroplastic glutathione pool
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Hemanth P.K. Sudhani , Joaquín Moreno
      The CO2-fixing activity of ribulose 1,5-bisphosphate carboxylase/oxygenase depends on the redox state of its cysteines. Disulfides like cystamine or 5,5′-dithio-bis(2-nitrobenzoic acid), but not oxidized glutathione, switch the enzyme to the inactive oxidized form. Conversely, thiols like cysteamine, cysteine, dithiotreitol or 2-mercaptoethanol, but not reduced glutathione, recover enzymatic activity after a previous oxidation. Direct regulation of the carboxylase activity by the chloroplastic glutathione pool is hindered by kinetic barriers impeding access to the critical residues. However, reduced glutathione can drive the recovery of activity by means of minute amounts of smaller intermediary thiol/disulfide exchangers. In contrast, oxidized glutathione does not inactivate the enzyme even in the presence of these intermediaries. This asymmetrical effect should help to maintain the enzyme in the active form in vivo.


      PubDate: 2015-01-19T17:11:57Z
       
  • Exploring allosteric activation of LigAB from Sphingobium sp. strain SYK-6
           through kinetics, mutagenesis and computational studies
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Kevin Patrick Barry , Abraham Ngu , Erin Frances Cohn , Joy Marie Cote , A. Maxwell Burroughs , Jason Paul Gerbino , Erika Anne Taylor
      The protocatechuate 4,5-dioxygenase (LigAB) from Sphingobium sp. strain SYK-6 is the defining member of the Type II extradiol dioxygenase superfamily (a.k.a. PCA Dioxygenase Superfamily or PCADSF) and plays a key aromatic ring-opening role in the metabolism of several lignin derived aromatic compounds. In our search for alternate substrates and inhibitors of LigAB, we discovered allosteric rate enhancement in the presence of non-substrate protocatechuate-like aldehydes such as vanillin. LigAB has the broadest substrate utilization profile of all protocatechuate (PCA) 4,5-dioxygenase described in the literature, however, the rate enhancement is only observed with PCA, with vanillin increasing k cat for LigAB by 36%. Computational docking has identified a potential site of allosteric binding near the entrance to the active site. Examination of a multiple sequence alignment reveals that many of the residues contributing to this newly identified allosteric pocket are highly conserved within the LigB family of the PCADSF. Point mutants of Phe103α and Ala18β, two residues located in the putative allosteric pocket, display altered rate enhancement as compared to LigAB-WT, providing support for the computationally identified allosteric binding site. Further investigation of this binding site may provide insight into the mechanism of this never before observed allosteric activation in extradiol dioxygenases.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • Design and characterization of a photo-activatable hedgehog probe that
           mimics the natural lipidated form
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Alan J. House , Laura R. Daye , Michael Tarpley , Kezia Addo , David S. Lamson , Margie K. Parker , Warren E. Bealer , Kevin P. Williams
      We have generated a photoactivatable form of sonic hedgehog protein by modifying the N-terminal cysteine with the heterobifunctional photocrosslinker 4-maleimidobenzophenone (Bzm). The Bzm modification on ShhN imparted a significant increase in activity as assessed in the C3H10T1/2 functional assay with potency comparable to that of the endogenous dual-lipidated form of ShhN (ShhNp). Reversed-phase HPLC analysis indicated that the increase in activity compared to unmodified ShhN may be due in part to the hydrophobic nature of the benzophenone group. In contrast to the fully processed ShhNp, Bzm-ShhN is monomeric as assessed by analytical SEC and does not require detergent to be soluble. Further, we demonstrated that the Bzm-ShhN was able to crosslink in vitro in the presence of a known binding partner, heparin. We suggest that Bzm-ShhN can serve as a relatively facile and preferred source of ShhNp for in vitro assays and as a probe to identify novel Hh protein interactions.


      PubDate: 2015-01-19T17:11:57Z
       
  • Aromaticity and amyloid formation: Effect of π-electron distribution
           and aryl substituent geometry on the self-assembly of peptides derived
           from hIAPP22–29
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Adam A. Profit , Jayson Vedad , Mohamad Saleh , Ruel Z.B. Desamero
      A comprehensive investigation of peptides derived from the 22–29 region of human islet amyloid polypeptide (hIAPP) that contain phenylalanine analogs at position 23 with a variety of electron donating and withdrawing groups, along with heteroaromatic surrogates, has been employed to interrogate how π-electron distribution effects amyloid formation. Kinetic aggregation studies using turbidity measurements indicate that electron rich aromatic ring systems consistently abolish the amyloidogenic propensity of hIAPP22–29. Electron poor systems modulate the rate of aggregation. Raman and Fourier transform infrared spectroscopy confirm the parallel β-sheet secondary structure of aggregates derived from peptides containing electron poor phenylalanine analogs and provide direct evidence of ring stacking. Transmission electron microscopy confirms the presence of amyloid fibrils. The effect of aryl substituent geometry on peptide self-assembly reveals that the electronic nature of substituents and not their steric profile is responsible for failure of the electron donating group peptides to aggregate. Non-aggregating hIAPP22–29 peptides were found to inhibit the self-assembly of full-length hIAPP1–37. The most potent inhibitory peptides contain phenylalanine with the p-amino and p-formamido functionalities. These novel peptides may serve as leads for the development of future aggregation inhibitors. A potential mechanism for inhibition of amylin self-assembly by electron rich hIAPP22–29 peptides is proposed.
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      PubDate: 2015-01-19T17:11:57Z
       
  • On the relationship between low-frequency normal modes and the large-scale
           conformational changes of proteins
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): Swapnil Mahajan , Yves-Henri Sanejouand
      Normal mode analysis is a computational technique that allows to study the dynamics of biological macromolecules. It was first applied to small protein cases, more than thirty years ago. The interest in this technique then raised when it was realized that it can provide insights about the large-scale conformational changes a protein can experience, for instance upon ligand binding. As it was also realized that studying highly simplified protein models can provide similar insights, meaning that this kind of analysis can be both quick and simple to handle, several applications were proposed, in the context of various structural biology techniques. This review focuses on these applications, as well as on how the functional relevance of the lowest-frequency modes of proteins was established.


      PubDate: 2015-01-19T17:11:57Z
       
  • Molecular characterization of cbfβ gene and identification of new
           transcription variants: Implications for function
    • Abstract: Publication date: 1 February 2015
      Source:Archives of Biochemistry and Biophysics, Volume 567
      Author(s): B. Simões , N. Conceição , A.C. Matias , J. Bragança , R.N. Kelsh , M.L. Cancela
      The CBFβ gene encodes a transcription factor that, in combination with CBFα (also called Runx, runt-related transcription factor) regulates expression of several target genes. CBFβ interacts with all Runx family members, such as RUNX2, a regulator of bone-related gene transcription that contains a conserved DNA-binding domain. CBFβ stimulates DNA binding of the Runt domain, and is essential for most of the known functions of RUNX2. A comparative analysis of the zebrafish cbfβ gene and protein, and of its orthologous identified homologous proteins in different species indicates a highly conserved function. We cloned eleven zebrafish cbfβ gene transcripts, one resulting in the known Cbfβ protein (with 187 aa), and three additional variants resulting from skipping exon 5a (resulting in a protein with 174 aa) or exon 5b (resulting in a protein with 201 aa), both observed for the first time in zebrafish, and a completely novel isoform containing both exon 5a and 5b (resulting in a protein with 188 aa). Functional analysis of these isoforms provides insight into their role in regulating gene transcription. From the other variants two are premature termination Cbfβ forms, while the others show in-frame exon-skipping causing changes in the Cbfβ domain that may affect its function.


      PubDate: 2015-01-19T17:11:57Z
       
  • Enhancing the heat stability and kinetic parameters of the maize endosperm
           ADP-glucose pyrophosphorylase using iterative saturation mutagenesis
    • Abstract: Publication date: Available online 16 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Susan K. Boehlein , Janine R. Shaw , Jon D. Stewart , Bradford Sullivan , L. Curtis Hannah
      Iterative saturation mutagenesis (ISM) has been used to improve the thermostability of maize endosperm ADP-glucose pyrophosphorylase (AGPase), a highly-regulated, rate-limiting and temperature-sensitive enzyme essential for starch biosynthesis. The thermo-sensitivity of heterotetrameric AGPase has been linked to grain loss in cereals and improving this property might therefore have direct impacts on grain yield. Nine amino acids were selected for site-saturation mutagenesis on the basis of elevated B-factors in the crystal structure of the closest available homolog (a small subunit homotetramer of potato AGPase). After each round of mutagenesis, iodine staining and antibody capture activity assays at varying temperatures were used to select the optimum positions and amino acid changes for the next rounds of mutagenesis. After three iterations, the signals from whole-colony iodine staining were saturated and a heat stable AGPase variant was obtained. Kinetic studies of the heat stable mutant showed that it also had an unexpected increased affinity for the activator, 3-PGA. This is particularly valuable as both the temperature stability and allosteric properties of AGPase significantly influence grain yield.


      PubDate: 2015-01-19T17:11:57Z
       
  • Hydrogen peroxide and hypochlorous acid influx through the major S.
           Typhimurium porin OmpD is affected by substitution of key residues of the
           channel
    • Abstract: Publication date: Available online 16 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Daniel Aguayo , Nicolás Pacheco , Eduardo H. Morales , Bernardo Collao , Roberto Luraschi , Carolina Cabezas , Paulina Calderon , Fernando D. González , Fernando Gil , Iván L. Calderón , Claudia P. Saavedra
      OmpD is the major Salmonella enterica serovar Typhimurium (S. Typhimurium) porin and mediates hydrogen peroxide (H2O2) influx. The results described herein extend this finding to hypochlorous acid (HOCl), another reactive oxygen species that is also part of the oxidative burst generated by the phagosome. S. Typhimurium cells lacking OmpD show decreased HOCl influx, and OmpD-reconstituted proteoliposomes show an increase in the uptake of the toxic compound. To understand this physiologically relevant process, we investigated the role of key OmpD residues in H2O2 and NaOCl transport. Using a theoretical approach, residue K16 was defined as a major contributor to the channel electrostatic properties, and E111 was shown to directly participate in the size-exclusion limit of the channel. Together, we provide theoretical, genetic, and biochemical evidence that OmpD mediates H2O2 and NaOCl uptake, and that key residues of the channel are implicated in this process.
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      PubDate: 2015-01-19T17:11:57Z
       
  • The Keap1–Nrf2 system and diabetes mellitus
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Akira Uruno , Yoko Yagishita , Masayuki Yamamoto
      Nrf2 (NF-E2-related factor 2) plays a key role in the protection of vertebrates against environmental stress by contributing to the inducible expression of detoxification and antioxidant enzymes. Keap1 (Kelch-like ECH-associated protein 1) is a sensor for oxidative and electrophilic stresses. Keap1 also acts as an E3 ubiquitin ligase substrate-recognition subunit that specifically targets Nrf2. Keap1 causes Nrf2 to be degraded through the ubiquitin–proteasome pathway and thus ensures that Nrf2 is constitutively suppressed under unstressed conditions. Upon exposure to oxidative or electrophilic stress, Keap1 loses its ability to ubiquitinate Nrf2. Many lines of evidence have recently clarified that the Keap1–Nrf2 system also plays critical roles in the maintenance of cellular homeostasis. One of the most salient examples is the contribution of Keap1–Nrf2 to metabolic and energy-balance regulation. In particular, how the Keap1–Nrf2 system protects the body against diabetes mellitus and how perturbations in this system provoke the disease condition are now under intense investigation. This review will summarize the recent progress made in this area.


      PubDate: 2015-01-19T17:11:57Z
       
  • The shikimate dehydrogenase family: Functional diversity within a
           conserved structural and mechanistic framework
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): James Peek , Dinesh Christendat
      Shikimate dehydrogenase (SDH) catalyzes the NADPH-dependent reduction of 3-deydroshikimate to shikimate, an essential reaction in the biosynthesis of the aromatic amino acids and a large number of other secondary metabolites in plants and microbes. The indispensible nature of this enzyme makes it a potential target for herbicides and antimicrobials. SDH is the archetypal member of a large protein family, which contains at least four additional functional classes with diverse metabolic roles. The different members of the SDH family share a highly similar three-dimensional structure and utilize a conserved catalytic mechanism, but exhibit distinct substrate preferences, making the family a particularly interesting system for studying modes of substrate recognition used by enzymes. Here, we review our current understanding of the biochemical and structural properties of each of the five previously identified SDH family functional classes.


      PubDate: 2015-01-19T17:11:57Z
       
  • Inhibition of bacterial mevalonate diphosphate decarboxylase by eriochrome
           compounds
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): D. Andrew Skaff , William J. McWhorter , Brian V. Geisbrecht , Gerald J. Wyckoff , Henry M. Miziorko
      Mevalonate diphosphate decarboxylase (MDD; EC 4.1.1.33) catalyzes the irreversible decarboxylation of mevalonate diphosphate in the mevalonate pathway to form isopentenyl diphosphate, which is a precursor in the biosynthesis of many essential polyisoprenoid natural products, including sterols. In low G/C Gram-positive bacteria, which utilize the mevalonate pathway, MDD is required for cell viability and thus is a potential target for development of antibiotic drugs. To identify potential inhibitors of the enzyme, the National Cancer Institute’s Mechanistic Diversity Set library of compounds was screened for inhibitors of Staphylococcus epidermidis MDD. From this screen, the compound Eriochrome Black A (EBA), an azo dye, was found to inhibit the enzyme with an IC50 value<5μM. Molecular docking of EBA into a crystal structure of S. epidermidis MDD suggested binding at the active site. EBA, along with the related Eriochrome B and T compounds, was evaluated for its ability to not only inhibit enzymatic activity but to inhibit bacterial growth as well. These compounds exhibited competitive inhibition towards the substrate mevalonate diphosphate, with Ki values ranging from 0.6 to 2.7μM. Non-competitive inhibition was observed versus ATP indicating binding of the inhibitor in the mevalonate diphosphate binding site, consistent with molecular docking predictions. Fluorescence quenching analyses also supported active site binding of EBA. These eriochrome compounds are effective at inhibiting S. epidermidis cell growth on both solid media and in liquid culture (MIC50 from 31 to 350μM) raising the possibility that they could be developed into antibiotic leads targeting pathogenic low-G/C Gram-positive cocci.
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      PubDate: 2015-01-19T17:11:57Z
       
  • Deciphering the interactions between chlorambucil and calf thymus DNA: A
           multi-spectroscopic and molecular docking study
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Sayeed Ur Rehman , Tarique Sarwar , Hassan Mubarak Ishqi , Mohammed Amir Husain , Ziaul Hasan , Mohammad Tabish
      Non-covalent interactions of chlorambucil with calf thymus DNA was investigated using multi-spectroscopic techniques and molecular docking study. Binding constant calculated was found to be 1.54×104 M−1 at 290K, significantly lower than various known intercalators. Quenching process was found to be static as evident by biomolecular quenching constant. Thermodynamic parameters revealed the involvement of hydrophobic interactions and hydrogen bonds in the binding. Chlorambucil was found to interact via external binding mode and follow groove binding as it replaces Hoechst (a typical groove binder) from the groove of DNA but does not replace intercalating dyes including ethidium bromide and acridine orange from the DNA helix. These results were further supported by KI quenching experiments, DNA melting studies, CD spectroscopy and molecular docking.


      PubDate: 2015-01-19T17:11:57Z
       
  • A salt-bridge stabilized C-terminal hook is critical for the dimerization
           of a Bowman Birk inhibitor
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Vinod Kumar , Saravanan Murugeson , Neha Vithani , Balaji Prakash , Lalitha R. Gowda
      Legume Bowman-Birk inhibitors (BBIs) that inhibit mammalian proteases exist as dimers in solution. The structural basis governing dimerization of HGI-III (horsegram seed BBI) was investigated. An intra-monomer salt bridge (D76–K71) stabilizes an atypical hook-like conformation at the C-terminus. We postulate that this hook, positions D75 to enable an inter-monomer salt-bridge D75a–K24b, which results in dimerization. We verify this by K71A and D76A mutations of HGI-III. The mutants were both monomers, likely due to destabilization of the C-terminal hook. Dimerization was sustained in a double mutant K71D/D76K that was anticipated to form a similar hook critical for dimerization. Conversely, K24b that interacts with D75a of the loop is the specificity determining residue that interacts with trypsin to inhibit its activity. The inter-monomer salt bridge D75a–K24b must be disrupted for the inhibition of trypsin, requiring HGI-III to transition into a monomer. Size exclusion studies and a model of HGI-III-trypsin complex support this notion. Interestingly, isoforms of the inhibitor present in germinated seeds (HGGIs) are monomers; and most strikingly, the C-termini of these inhibitors are truncated with the loss the C-terminal hook critical for dimerization. The tendency of HGI-III to self-associate seems to relate to its physiological function of a storage protein.
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      PubDate: 2015-01-19T17:11:57Z
       
  • Palmitate induces insulin resistance in human HepG2 hepatocytes by
           enhancing ubiquitination and proteasomal degradation of key insulin
           signaling molecules
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Megumi Ishii , Ayumi Maeda , Shuji Tani , Mitsugu Akagawa
      Obesity-associated insulin resistance is a major pathogenesis of type 2 diabetes mellitus and is characterized by defects in insulin signaling. High concentrations of plasma free fatty acids (FFAs) are involved in the etiology of obesity-associated insulin resistance. However, the detailed mechanism by which FFAs contribute to the development of insulin resistance is not yet fully understood. We investigated the molecular basis of insulin resistance elicited by FFAs using the human hepatocyte cell line HepG2. Among major human FFAs, palmitate markedly inhibited insulin-stimulated phosphorylation of key insulin signaling molecules such as insulin receptor, insulin receptor substrate-1, and Akt, indicating that palmitate is the principal inducer of insulin resistance. We revealed that palmitate facilitates ubiquitination of the key insulin signaling molecules, and subsequently elicits their proteasomal degradation. Furthermore, we demonstrated that inhibition of ubiquitination by the ubiquitin-activating enzyme E1 inhibitor PYR41 significantly prevents palmitate-inducible insulin resistance but not by the proteasome inhibitor MG132, implying that ubiquitinated signaling molecules may be dysfunctional. In conclusion, inhibition of ubiquitination of the key insulin signaling molecules may be a potential strategy for preventing and treating obesity-associated insulin resistance.


      PubDate: 2015-01-19T17:11:57Z
       
  • Structural characterization of the catalytic site of a Nilaparvata lugens
           delta-class glutathione transferase
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Kohji Yamamoto , Akifumi Higashiura , MD. Tofazzal Hossain , Naotaka Yamada , Takahiro Shiotsuki , Atsushi Nakagawa
      Glutathione transferases (GSTs) are a major class of detoxification enzymes that play a central role in the defense against environmental toxicants and oxidative stress. Here, we studied the crystal structure of a delta-class glutathione transferase from Nilaparvata lugens, nlGSTD, to gain insights into its catalytic mechanism. The structure of nlGSTD in complex with glutathione, determined at a resolution of 1.7Å, revealed that it exists as a dimer and its secondary and tertiary structures are similar to those of other delta-class GSTs. Analysis of a complex between nlGSTD and glutathione showed that the bound glutathione was localized to the glutathione-binding site. Site-directed mutagenesis of nlGSTD mutants indicated that amino acid residues Ser11, His52, Glu66, and Phe119 contribute to catalytic activity.


      PubDate: 2015-01-19T17:11:57Z
       
  • Tumor necrosis factor-α-induced apoptosis of gastric cancer MKN28
           cells: Accelerated degradation of the inhibitor of apoptosis family
           members
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Maki Kitagawa , Atsushi Shiozaki , Daisuke Ichikawa , Shingo Nakashima , Toshiyuki Kosuga , Hirotaka Konishi , Shuhei Komatsu , Hitoshi Fujiwara , Kazuma Okamoto , Eigo Otsuji
      The role of the inhibitor of apoptosis (IAP) family members in tumor necrosis factor-α (TNF-α)-induced apoptosis of human gastric cancer MKN28 cells was explored. TNF-α induced up-regulation of cIAP2, whereas cycloheximide (CHX) induced down-regulation of XIAP and survivin. Degradation of cIAP1 and XIAP, but not survivin, was accelerated by co-treatment of cells with TNF-α and CHX, and TNF-α-induced up-regulation of cIAP2 was inhibited by BMS-345541 (NF-κB inhibitor). Treatment of MKN28 cells with TNF-α plus CHX induced degradation of survivin and activation of caspase-8 and -3, followed by degradation of cIAP1 and XIAP and apoptosis. Proteasome inhibitors (MG132 and epoxomicin) suppressed TNF-α plus CHX-induced degradation of survivin, cIAP1, and XIAP as well as apoptosis. A caspase inhibitor (z-VAD-fmk) suppressed TNF-α plus CHX-induced apoptosis, but allowed degradation of survivin, cIAP1 and XIAP. TNF-α receptor 1 and 2 were expressed on MKN28 cells. The magnitude of apoptosis induced by TNF-α plus BMS-345541 was much less than that induced by TNF-α plus CHX. These findings suggest that TNF-α plus CHX-induced apoptosis of gastric cancer MKN28 cells may be caused by accelerated degradation of the IAP family members (survivin, cIAP1, and XIAP), in addition to inhibition of NF-κB-dependent synthesis of anti-apoptotic molecules.


      PubDate: 2015-01-19T17:11:57Z
       
  • Regulation of myofibroblast differentiation by miR-424 during
           epithelial-to-mesenchymal transition
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Xiao Xiao , Chaoqun Huang , Chunling Zhao , Xuxu Gou , Lakmini K. Senavirathna , Myron Hinsdale , Pamela Lloyd , Lin Liu
      Idiopathic pulmonary fibrosis (IPF) is one of the most common and severe interstitial lung diseases. Epithelial-to-mesenchymal transition (EMT) is a process whereby epithelial cells undergo transition to a mesenchymal phenotype. This process has been shown to contribute to IPF. MicroRNAs (miRNAs) are small non-coding RNAs of 18–24 nucleotides in length which regulate gene expression. Several studies have implicated miRNAs in EMT; however, specific miRNAs that regulate EMT in IPF have not yet been identified. In this study, we identified 6 up-regulated and 3 down-regulated miRNAs in a human lung epithelial cell EMT model using miRNA microarray and real-time PCR. Overexpression of one of these up-regulated miRNAs, miR-424, increased the expression of α-smooth muscle actin, an indicator of myofibroblast differentiation, but had no effects on the epithelial or mesenchymal cell markers. miR-424 enhanced the activity of the TGF-β signaling pathway, as demonstrated by a luciferase reporter assay. Further experiments showed that miR-424 decreased the protein expression of Smurf2, a negative regulator of TGF-β signaling, indicating that miR-424 exerts a forward regulatory loop in the TGF-β signaling pathway. Our results suggest that miR-424 regulates the myofibroblast differentiation during EMT by potentiating the TGF-β signaling pathway, likely through Smurf2.


      PubDate: 2015-01-19T17:11:57Z
       
  • PI3K/AKT and Mdm2 activation are associated with inhibitory effect of cAMP
           increasing agents on DNA damage-induced cell death in human pre-B NALM-6
           cells
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Arman Ghorbani , Mahmood Jeddi-Tehrani , Atoosa Saidpour , Majid Safa , Ahmad Ali Bayat , Hamid Zand
      DNA damage response (DDR) consists of both proapoptotic and prosurvival signaling branches. Superiority of each signaling branch determines the outcome of DNA damage: death or allowing the repair. The present authors have previously shown that an increased intracellular level of cAMP disrupts p53-mediated apoptosis in human pre-B NALM-6 cells and inhibition of NF-κB prevents prosurvival effect of cAMP during DNA damage. AKT/PKB (protein kinase B) is a general mediator of survival signaling. AKT signaling inhibits p53-mediated transcription and apoptosis. The results of present study showed that cAMP disrupted DNA damage/p53-mediated apoptosis through AKT and subsequent NF-κB activation. These results suggested that AKT may be found as part of a complex with scaffolding proteins, beta-arrestins and PDE4D. cAMP disarticulated the complex through binding to PDE4D compartment. It seems that release of AKT protein potentiated DDR activated pro-survival AKT in NALM-6 cells. Taken together, the present data indicated that regulation of AKT signaling may determine the fate of cells exposed to genotoxic stress.
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      PubDate: 2015-01-19T17:11:57Z
       
  • Tellurite-mediated damage to the Escherichia coli NDH-dehydrogenases and
           terminal oxidases in aerobic conditions
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Waldo A. Díaz-Vásquez , María J. Abarca-Lagunas , Fabián A. Cornejo , Camilo A. Pinto , Felipe A. Arenas , Claudio C. Vásquez
      Escherichia coli exposed to tellurite shows augmented membrane lipid peroxidation and ROS content. Also, reduced thiols, protein carbonylation, [Fe–S] center dismantling, and accumulation of key metabolites occur in these bacteria. In spite of this, not much is known about tellurite effects on the E. coli electron transport chain (ETC). In this work, tellurite-mediated damage to the E. coli ETC’s NADH dehydrogenases and terminal oxidases was assessed. Mutant lacking ETC components showed delayed growth, decreased oxygen consumption and increased ROS in the presence of the toxicant. Membranes from tellurite-exposed E. coli exhibited decreased oxygen consumption and dNADH/NADH dehydrogenase activity, showing an impairment of NDH-I but not of NDH-II activity. Regarding terminal oxidases, only the bo oxidase complex was affected by tellurite. When assaying NDH-I and NDH-II activity in the presence of superoxide, the NDH-I complex was preferentially damaged. The activity was partly restored in the presence of reducing agents, sulfide and Fe2+ under anaerobic conditions, suggesting that damage affects NDH-I [4Fe–4S] centers. Finally, augmented membrane protein oxidation along with reduced oxidase activity was observed in the presence of the toxicant. Also, the increased expression of genes encoding alternative terminal oxidases probably reflects a cell’s change towards anaerobic respiration when facing tellurite.


      PubDate: 2015-01-19T17:11:57Z
       
  • Monoterpene (−)-citronellal affects hepatocarcinoma cell signaling
           via an olfactory receptor
    • Abstract: Publication date: 15 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 566
      Author(s): Désirée Maßberg , Annika Simon , Dieter Häussinger , Verena Keitel , Günter Gisselmann , Heike Conrad , Hanns Hatt
      Terpenes are the major constituents of essential oils in plants. In recent years, terpenes have become of clinical relevance due to their ability to suppress cancer development. Their effect on cellular proliferation has made them promising agents in the prevention or treatment of many types of cancer. In the present study, a subset of different monoterpenes was investigated for their molecular effects on the hepatocellular carcinoma cell line Huh7. Using fluorometric calcium imaging, acyclic monoterpene (−)-citronellal was found to induce transient Ca2+ signals in Huh7 cells by activating a cAMP-dependent signaling pathway. Moreover, we detected the (−)-citronellal-activated human olfactory receptor OR1A2 at the mRNA and protein levels and demonstrated its potential involvement in (−)-citronellal-induced calcium signaling in Huh7 cells. Furthermore, activation of OR1A2 results in phosphorylation of p38 MAPK and reduced cell proliferation, indicating an effect on hepatocellular carcinoma progression. Here, we provide for the first time data on the molecular mechanism evoked by (−)-citronellal in human hepatocellular carcinoma cells. The identified olfactory receptor could serve as a potential therapeutic target for cancer diagnosis and treatment.


      PubDate: 2015-01-19T17:11:57Z
       
  • Stability of bacterial carotenoids in the presence of iron in a model of
           the gastric compartment – Comparison with dietary reference
           carotenoids
    • Abstract: Publication date: Available online 13 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Charlotte Sy , Olivier Dangles , Patrick Borel , Catherine Caris-Veyrat
      Recently isolated spore-forming pigmented marine bacteria, Bacillus indicus HU36 and Bacillus firmus GB1 are sources of carotenoids (∼fifteen distinct yellow and orange pigments and ∼thirteen distinct pink pigments, respectively). They are glycosides of oxygenated lycopene derivatives (apo-lycopenoids) and are assumed to be more heat- and gastric-stable than common carotenoids. In this study, the oxidation by O2 of the bacterial carotenoids was initiated by free iron (FeII and FeIII) or by heme iron (metmyoglobin) in a mildly acidic aqueous solution mimicking the gastro-intestinal compartment and compared to the oxidation of the common dietary carotenoids β-carotene, lycopene and astaxanthin. Under these conditions, all bacterial carotenoids appear more stable in the presence of heme iron vs. free iron. Carotenoid autoxidation initiated by FeII is relatively fast and likely involves reactive oxygen–iron species derived from FeII and O2. By contrast, the corresponding reaction with FeIII is kinetically blocked by the slow preliminary reduction of FeIII into FeII by the carotenoids. The stability of carotenoids toward autoxidation increases as follows: β-carotene<lycopene<astaxanthin<HU36 and GB1. In particular, bacterial carotenoids react more quickly than reference carotenoids with FeIII, but much more slowly than the reference carotenoids with FeII. This reaction is correlated with the structure of the carotenoids, which can have opposite effects in a micellar system: bacterial carotenoids with electro-attracting terminal groups have a lower reducing capacity than β-carotene and lycopene. However, their polar head favours their location close to the interface of micelles, in closer contact with oxidative species. Kinetic analyses of the iron-induced autoxidation of astaxanthin and HU36 carotenoids has been performed and gives insights in the underlying mechanisms.


      PubDate: 2015-01-19T17:11:57Z
       
  • Dietary tomato powder inhibits alcohol-induced hepatic injury by
           suppressing cytochrome p450 2E1 induction in rodent models
    • Abstract: Publication date: Available online 12 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Camilla P. Stice , Chun Liu , Koichi Aizawa , Andrew S. Greenberg , Lynne M. Ausman , Xiang-Dong Wang
      Chronic and excessive alcohol consumption leads to the development of alcoholic liver disease (ALD) and greatly increases the risk of liver cancer. Induction of the cytochrome p450 2E1 (CYP2E1) enzyme by chronic and excessive alcohol intake is known to play a role in the pathogenesis of ALD. High intake of tomatoes, rich in the carotenoid lycopene, is associated with a decreased risk of chronic disease. We investigated the effects of whole tomato (tomato powder, TP), partial tomato (tomato extract, TE), and purified lycopene (LYC) against ALD development in rats. Of the three supplements, only TP reduced the severity of alcohol-induced steatosis, hepatic inflammatory foci, and CYP2E1 protein levels. TE had no effect on these outcomes and LYC greatly increased inflammatory foci in alcohol-fed rats. To further support the protective effect of TP against ALD, TP was supplemented in a carcinogen (diethylnitrosamine, DEN)-initiated alcohol-promoted mouse model. In addition to reduced steatosis and inflammatory foci, TP abolished the presence of preneoplastic foci of altered hepatocytes in DEN-injected mice fed alcohol. These reductions were associated with decreased hepatic CYP2E1 protein levels, restored levels of peroxisome proliferator-activated receptor-α and downstream gene expression, decreased inflammatory gene expression, and reduced endoplasmic reticulum stress markers. These data provide strong evidence for TP as an effective whole food prevention strategy against ALD.


      PubDate: 2015-01-19T17:11:57Z
       
  • TGFβ1 rapidly activates Src through a non-canonical redox signaling
           mechanism
    • Abstract: Publication date: Available online 10 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Hongqiao Zhang , Kelvin J.A. Davies , Henry Jay Forman
      Transforming growth factor-β1 (TGF-β) is involved in multiple cellular processes through Src activation. In the canonical pathway, Src activation is initiated by pTyr530 dephosphorylation followed by a conformational change allowing Tyr419 auto-phosphorylation. A non-canonical pathway in which oxidation of cysteine allows bypassing of pTyr530 dephosphorylation has been reported. Here, we examined how TGF-β activates Src in H358 cells, a small cell lung carcinoma cell line. TGF-β increased Src Tyr419 phosphorylation, but surprisingly, Tyr530 phosphorylation was increased rather than decreased. Vanadate, a protein tyrosine phosphatase inhibitor, stimulated Src activation itself, but rather than inhibiting Src activation by TGF-β, activation by vanadate was additive with TGF-β showing that pTyr530 dephosphorylation was not required. Thus, the involvement of the non-canonical oxidative activation was suspected. TGF-β increased extracellular H2O2 transiently while GSH-ester and catalase abrogated Src activation by TGF-β. Apocynin, a NADPH oxidase inhibitor, inhibited TGF-β-stimulated H2O2 production. Furthermore, mutation of cysteines to alanine, 248C/A, 277C/A, or 501C/A abrogated, while 490C/A significantly reduced, TGF-β-mediated Src activation. Taken together, the results indicate that TGF-β-mediated Src activation operates largely through a redox dependent mechanism, resulting from enhanced H2O2 production through an NADPH oxidase and that cysteines 248, 277, 490, and 501 are critical for this activation.


      PubDate: 2015-01-19T17:11:57Z
       
  • Tauroursodeoxycholic acid prevents stress induced aggregation of proteins
           in vitro and promotes PERK activation in HepG2 cells
    • Abstract: Publication date: Available online 8 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Amina R. Gani , Jagadeesh Kumar Uppala , V.A. Ramaiah Kolluru
      Tauroursodeoxycholic acid (TUDCA) a bile salt and chemical chaperone reduces stress-induced aggregation of proteins; activates PERK [PKR (RNA-dependent protein kinase)-like ER (endoplasmic reticulum) kinase] or EIF2AK3, one of the hall marks of ER stress induced unfolded protein response (UPR) in human hepatoblastoma HepG2 cells; prevents heat and dithiothreitol (DTT) induced aggregation of BSA (bovine serum albumin), and reduces ANS (1-anilino-naphthalene-8-sulfonate) bound BSA fluorescence in vitro. TUDCA inactivates heat treated, but not the native EcoR1 enzyme, and reduces heat-induced aggregation and activity of COX-1 (cyclooxygenase enzyme-1) in vitro. These findings suggest that TUDCA binds to the hydrophobic regions of proteins and prevent their subsequent aggregation. This may stabilize unfolded proteins that can mount UPR or facilitate their degradation through cellular degradation pathways.


      PubDate: 2015-01-19T17:11:57Z
       
  • A chain extension method for apocarotenoids; lycopene and lycophyll
           syntheses
    • Abstract: Publication date: Available online 8 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Jeongae Choi , Eun-Taek Oh , Sangho Koo
      The novel C5 benzothiazolyl (BT) sulfone containing an acetal group was prepared as a building block for the chain-extension of apocarotenoids. The double Julia–Kocienski olefination of the BT-sulfone with C10 2,7-dimethyl-2,4,6-octatrienedial and deprotection of the resulting acetal groups efficiently produced C20 crocetin dial. The higher homologues of C30 and C40 apocarotenoids were prepared from C20 crocetin dial by the repeated application of the Julia–Kocienski olefination of the C5 BT-sulfone and hydrolysis. The scopes of the Julia–Kocienski olefination in the total synthesis of carotenoid natural products were evaluated using the C10 +C20 +C10 coupling protocol. The olefination was sensitive to the steric factor and bulky C10 β-cyclogeranyl BT-sulfone was not able to react with C20 crocetin dial, however, lycopene and lycophyll were efficiently produced by the Julia–Kocienski olefination of C10 geranyl BT-sulfone and hydroxygeranyl BT-sulfone, in which protection of the hydroxyl group was not necessary.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • Recent progress in molecular genetic studies on the carotenoid transport
           system using cocoon-color mutants of the silkworm
    • Abstract: Publication date: Available online 8 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Kozo Tsuchida , Takashi Sakudoh
      The existence of tissue-specific delivery for certain carotenoids is supported by genetic evidence from the silkworm Bombyx mori and the identification of cocoon color mutant genes, such as Yellow blood (Y), Yellow cocoon (C), and Flesh cocoon (F). Mutants with white cocoons are defective in one of the steps involved in transporting carotenoids from the midgut lumen to the middle silk gland via the hemolymph lipoprotein, lipophorin, and the different colored cocoons are caused by the accumulation of specific carotenoids into the middle silk gland. The Y gene encodes carotenoid-binding protein (CBP), which is expected to function as the cytosolic transporter of carotenoids across the enterocyte and epithelium of the middle silk gland. The C and F genes encode the C locus-associated membrane protein, which is homologous to a mammalian high-density lipoprotein receptor-2 (Cameo2) and scavenger receptor class B member 15 (SCRB15), respectively; these membrane proteins are expected to function as non-internalizing lipophorin receptors in the middle silk gland. Cameo2 and SCRB15 belong to the cluster determinant 36 (CD36) family, with Cameo2 exhibiting specificity not only for lutein, but also for zeaxanthin and astaxanthin, while SCRB15 seems to have specificity toward carotene substrates such as α-carotene and β-carotene. These findings suggest that Cameo2 and SCRB15 can discriminate the chemical structure of lutein and β-carotene from circulating lipophorin during uptake. These data provide the first evidence that CD36 family proteins can discriminate individual carotenoid molecules in lipophorin.


      PubDate: 2015-01-19T17:11:57Z
       
  • Cellular localization of β-carotene 15,15′ oxygenase-1 (BCO1)
           and β-carotene 9′,10′ oxygenase-2 (BCO2) in rat liver and
           intestine
    • Abstract: Publication date: Available online 6 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Shiva Raghuvanshi , Vanessa Reed , William S. Blaner , Earl H. Harrison
      The intestine and liver are crucial organs for vitamin A uptake and storage. Liver accounts for 70% of total body retinoid stores. Vitamin A deficiency (VAD) is a major micronutrient deficiency around the world. The provitamin A carotenoid, β-carotene, is a significant source of vitamin A in the diet. β-Carotene 15,15′ oxygenase-1 (BCO1) and β-carotene 9′,10′ oxygenase-2 (BCO2) are the two known carotenoid cleavage enzymes in humans. BCO1 and BCO2 are highly expressed in liver and intestine. Hepatocytes and hepatic stellate cells are two main cell types involved in the hepatic metabolism of retinoids. Stellate-like cells in the intestine also show ability to store vitamin A. Liver is also known to accumulate carotenoids, however, their uptake, retention and metabolism in specific liver and intestinal cell types is still unknown. Hence, we studied the cellular and subcellular expression and localization of BCO1 and BCO2 proteins in rat liver and intestine. We demonstrate that both BCO1 and BCO2 proteins are localized in hepatocytes and mucosal epithelium. We also show that BCO1 is also highly expressed in hepatic stellate cells (HSC) and portal endothelial cells in liver. At the subcellular level in liver, BCO1 is found in cytosol, while BCO2 is found in mitochondria. In intestine, immunohistochemistry showed strong BCO1 immunoreactivity in the duodenum, particularly in Brunner’s glands. Both BCO1 and BCO2 showed diffuse presence along epithelia with strong immunoreactivity in endothelial cells and in certain epithelial cells which warrant further investigation as possible intestinal retinoid storage cells.


      PubDate: 2015-01-19T17:11:57Z
       
  • Obesity-induced oxidative stress, accelerated functional decline with age
           and increased mortality in mice
    • Abstract: Publication date: Available online 2 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Yiqiang Zhang , Kathleen E. Fischer , Vanessa Soto , Yuhong Liu , Danuta Sosnowska , Arlan Richardson , Adam B. Salmon
      Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process.


      PubDate: 2015-01-19T17:11:57Z
       
  • Characterisation of Dyp-type peroxidases from Pseudomonas fluorescens
           Pf-5: Oxidation of Mn(II) and polymeric lignin by Dyp1B
    • Abstract: Publication date: Available online 2 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Rahman Rahmanpour , Timothy D.H. Bugg
      Members of the DyP family of peroxidases in Gram-positive bacteria have recently been shown to oxidise Mn(II) and lignin model compounds. Gram-negative pseudomonads, which also show activity for lignin oxidation, also contain dyp-type peroxidase genes. Pseudomonas fluorescens Pf-5 contains three dyp-type peroxidases (35, 40 and 55kDa), each of which has been overexpressed in Escherichia coli, purified, and characterised. Each of the three enzymes shows activity for oxidation of phenol substrates, but the 35kDa Dyp1B enzyme also shows activity for oxidation of Mn(II) and Kraft lignin. Treatment of powdered lignocellulose with Dyp1B in the presence of Mn(II) and hydrogen peroxide leads to the release of a low molecular weight lignin fragment, which has been identified by mass spectrometry as a β-aryl ether lignin dimer containing one G unit and one H unit bearing a benzylic ketone. A mechanism for release of this fragment from lignin oxidation is proposed.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • Targeting acidity in diseased tissues: Mechanism and applications of the
           membrane-inserting peptide, pHLIP
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): John C. Deacon , Donald M. Engelman , Francisco N. Barrera
      pHLIPs are a family of soluble ∼36 amino acid peptides, which bind to membrane surfaces. If the environment is acidic, a pHLIP folds and inserts across the membrane to form a stable transmembrane helix, thus preferentially locating itself in acidic tissues. Since tumors and other disease tissues are acidic, pHLIPs’ low-pH targeting behavior leads to applications as carriers for diagnostic and surgical imaging agents. The energy of membrane insertion can also be used to promote the insertion of modestly polar, normally cell-impermeable cargos across the cell membrane into the cytosol of targeted cells, leading to applications in tumor-targeted delivery of therapeutic molecules. We review the biochemical and biophysical basis of pHLIPs’ unique properties, diagnostic and therapeutic applications, and the principles upon which translational applications are being developed.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular
           signaling pathway in human hepatocellular carcinoma cells
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): Tomoaki Nagasawa , Rie Matsushima-Nishiwaki , Eisuke Yasuda , Junya Matsuura , Hidenori Toyoda , Yuji Kaneoka , Takashi Kumada , Osamu Kozawa
      We previously demonstrated that the expression of HSP20, a small heat shock protein, is inversely correlated with the progression of HCC. Inflammation is associated with HCC, and numerous cytokines, including TNF-α, act as key mediators in the progression of HCC. In the present study, we investigated whether HSP20 is implicated in the TNF-α-stimulated intracellular signaling in HCC using human HCC-derived HuH7 cells in the presence of TNF-α. In HSP20-overexpressing HCC cells, the cell growth was retarded compared with that in the control cells under long-term exposure of TNF-α. Because NF-κB pathway is the main intracellular signaling system activated by TNF-α, we investigated the effects of HSP20-overexpression of this pathway. The protein levels of IKK-α, but not IKK-β, in the HSP20-overexpressing cells were decreased. Short-term exposure to TNF-α-induced phosphorylation and degradation of IκB, and the phosphorylation and transactivational activity of NF-κB were suppressed in the HSP20-overexpressing HCC cells. Furthermore, the increase in IKK-α levels was accompanied by a decrease in the HSP20 levels in human HCC tissues. These findings strongly suggest that HSP20 might decrease the IKK-α protein level and that it down-regulates the TNF-α-stimulated intracellular signaling in HCC, thus resulting in the suppression of HCC progression.


      PubDate: 2015-01-19T17:11:57Z
       
  • Isolation and characterization of a protease inhibitor from Acacia karroo
           with a common combining loop and overlapping binding sites for
           chymotrypsin and trypsin
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): András Patthy , Tamás Molnár , Pálma Porrogi , Ryno Naudé , László Gráf
      By using affinity and reversed-phase HPLC (RP-HPLC) chromatographies two chymotrypsin–trypsin inhibitors were isolated from seeds of Acacia karroo, a legume of the subfamily Mimosoideae. The primary structure of one of these inhibitors, named AkCI/1, was determined. The inhibitor consists of two polypeptide chains, 139 and 44 residues respectively, which are linked by a single disulfide bridge. The amino acid sequence of AkCI/1 is homologous to and showed more than 60% sequence similarity with other protease inhibitors isolated earlier from the group of Mimosoideae. AkCI/1 inhibits both chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) in a 1:1M ratio with K i values of 2.8×10−12 M and 1.87×10−12 M, respectively. The P1–P1′ residues for trypsin were identified as Arg68-Ile69 by selective hydrolysis of the inhibitor at this site, with bovine trypsin and human trypsin IV. The cleavage did not affect the inhibition of trypsin, but fully abolished the chymotrypsin inhibitory activity of AkCI/1. This finding together with our studies on competition of the two enzymes for the same combining loop suggests that the same loop has to contain the binding sites for both proteases. The most likely P1 residue of AkCI/1 for chymotrypsin is Tyr67.


      PubDate: 2015-01-19T17:11:57Z
       
  • Leukotriene signaling in the extinct human subspecies Homo denisovan and
           Homo neanderthalensis. Structural and functional comparison with Homo
           sapiens
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): Susan Adel , Kumar Reddy Kakularam , Thomas Horn , Pallu Reddanna , Hartmut Kuhn , Dagmar Heydeck
      Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies.
      Graphical abstract image

      PubDate: 2015-01-19T17:11:57Z
       
  • Heme binds to an intrinsically disordered region of Bach2 and alters its
           conformation
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): Miki Watanabe-Matsui , Takashi Matsumoto , Toshitaka Matsui , Masao Ikeda-Saito , Akihiko Muto , Kazutaka Murayama , Kazuhiko Igarashi
      The transcriptional repressor Bach2 regulates humoral and cellular immunity, including antibody class switching. It possesses a basic leucine zipper domain that mediates DNA binding. Heme inhibits the DNA-binding activity of Bach2 in vitro and induces the degradation of Bach2 in B cells. However, the structural basis of the heme–Bach2 interaction has not been identified. Spectroscopic analyses revealed that Bach2331–520 is the heme-binding domain, as it includes three Cys-Pro motifs known to be important for heme binding. Heme-titration experiments demonstrated the presence of 5- and 6-coordinated heme-binding modes. Circular dichroism measurements indicated that Bach2331–520 exists mostly in a random-coil conformation. However, dynamic light scattering analyses showed that, upon heme binding to Bach2331–520, this region becomes denatured at a lower temperature, as compared with unbound Bach2331–520. In addition, small-angle X-ray scattering and chemical modification analyses revealed that heme binding induces conformational alterations within the unstructured region. A GAL4-based luciferase assay in 293T cells showed that heme alters the protein interactions mediated by Bach2331–520. These observations suggested that the unstructured region of Bach2 is important for heme binding, and consequently for its functional regulation.


      PubDate: 2015-01-19T17:11:57Z
       
  • CRLI induces vascular smooth muscle relaxation and suggests a dual
           mechanism of eNOS activation by legume lectins via muscarinic receptors
           and shear stress
    • Abstract: Publication date: 1 January 2015
      Source:Archives of Biochemistry and Biophysics, Volume 565
      Author(s): Bruno A.M. Rocha , Ito L. Barroso-Neto , Claudener S. Teixeira , Mayara Q. Santiago , Alana F. Pires , Luiz A.G. Souza , Kyria S. Nascimento , Alexandre H. Sampaio , Plinio Delatorre , Ana M.S. Assreuy , Benildo S. Cavada
      Lectins are proteins able to recognize carbohydrates, without modifying their structure, via the carbohydrate-recognition domain (CRD). Here, the three-dimensional structure of the mannose-binding lectin isolated from Cymbosema roseum (CRLI) was determined with X-man molecule modeled into the carbohydrate recognition domain. CRLI relaxant activity in thoracic rat aorta was also investigated, and based on the results, a molecular docking of CRLI with heparan sulfate was performed to investigate the possible interaction with mechanoreceptors involved in vasorelaxation. CRLI (IC50 = 12.4μgmL − 1) elicited vasorelaxant response (96%) in endothelialized rat aorta contracted with phenylephrine. Endothelium-derived relaxant factors, extracellular calcium (Ca2+ e) and muscarinic receptors were also evaluated as putative participants in the CRLI relaxant effect. CRLI relaxant effect was blocked by L-NAME, a nonselective inhibitor of nitric oxide synthase (NOS), and partially inhibited in a calcium-free solution (0Ca) and by atropine, but it remained unchanged in the presence of indomethacin and TEA. In summary, our data suggest interaction between CRLI and muscarinic receptors located in vascular endothelial cells leading to NOS activation triggered by a mechanism that involves Ca2+ e along with the ability of CRLI to interact with heparan sulfate, a highly rated mechanoreceptor involved in eNOS activation.


      PubDate: 2015-01-19T17:11:57Z
       
  • Independent evolution of four heme peroxidase superfamilies
    • Abstract: Publication date: Available online 6 January 2015
      Source:Archives of Biochemistry and Biophysics
      Author(s): Marcel Zámocký , Stefan Hofbauer , Irene Schaffner , Bernhard Gasselhuber , Andrea Nicolussi , Monika Soudi , Katharina F. Pirker , Paul G. Furtmüller , Christian Obinger
      Four heme peroxidase superfamilies (peroxidase–catalase, peroxidase–cyclooxygenase, peroxidase–chlorite dismutase and peroxidase–peroxygenase superfamily) arose independently during evolution, which differ in overall fold, active site architecture and enzymatic activities. The redox cofactor is heme b or posttranslationally modified heme that is ligated by either histidine or cysteine. Heme peroxidases are found in all kingdoms of life and typically catalyze the one- and two-electron oxidation of a myriad of organic and inorganic substrates. In addition to this peroxidatic activity distinct (sub)families show pronounced catalase, cyclooxygenase, chlorite dismutase or peroxygenase activities. Here we describe the phylogeny of these four superfamilies and present the most important sequence signatures and active site architectures. The classification of (sub)families is described as well as important turning points in evolution. We show that at least three heme peroxidase superfamilies have ancient prokaryotic roots with several alternative ways of divergent evolution. In later evolutionary steps, they almost always produced highly evolved and specialized clades of peroxidases in eukaryotic kingdoms with a significant portion of such genes involved in coding various fusion proteins with novel physiological functions.
      Graphical abstract image

      PubDate: 2015-01-09T09:26:03Z
       
 
 
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