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s-adenosyl-l-methionine towards hepatitis C virus expression: Need to consider s-adenosyl-l-methionine's chemistry, physiology and pharmacokinetics

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World Journal of Gastroenterology 2017年第40期23卷 7343-7346页

作者： Dimitrios Tsikas Erik Hanff Alexander Bollenbach Core Unit Proteomics Hannover Medical School

s-adenosyl-l-methionine(sAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that sAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells at millimolar concentrations. The efficacy of sAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated.

关键词： s-adenosyl-l-methionine Bioavailability Concentration liver

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Hepatoprotective effects of s-adenosyl-l-methionine against alcohol-and cytochrome P450 2E1-induced liver injury

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World Journal of Gastroenterology 2010年第11期16卷 1366-1376页

作者： Arthur I Cederbaum Department of Pharmacology and systems Therapeutics Box 1603 Mount Sinai School of Medicine One Gustave Levy Place

s-adenosyl-l-methionine (sAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. sAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic sAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by sAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.

关键词： Cytochrome P450 2E1 s-adenosyl-l-methionine Ethanol Toxic hepatitis Oxidative stress

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s-adenosyl-l-methionine modifies antioxidant-enzymes,glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells

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World Journal of Gastroenterology 2016年第14期22卷 3746-3757页

作者： sonia Amelia lozano-sepulveda Eduardo Bautista-Osorio Jose Angel Merino-Mascorro Marta Varela-Rey linda Elsa Munoz-Espinosa Paula Cordero-Perez María luz Martinez-Chantar Ana Maria Rivas-Estilla Department of Biochemistry and Molecular Medicine School of Medicine Autonomous University of Nuevo Leon Monterrey Metabolomic Unit CIC bio GUNE CIBERehd Parque Tecnológico de Bizkaia liver Unit School of Medicine and Hospital Universitario Autonomous University of Nuevo Leon

AIM: To elucidate the mechanism(s) by which s-adenosyl-l-methionine(sAM) decreases hepatitis C virus(HCV) ***: We examined the effects of sAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/l sAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(sOD-1, sOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPs18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-Ns5 A, sOD-1, sOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROs) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant ***: sAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). sAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/l sAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon sAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(sOD-1, sOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROs levels upon sAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon sAM treatment a

关键词： Hepatitis C virus s-adenosyl-l-methionine superoxide dismutase 1 superoxide dismutase 2 Replication Hepatitis C virus-RNA Ns5A Oxidative stress Antioxidants Viral proteins Reactive oxygen species Pyrrolidine dithiocarbamate

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A screening strategy of *** mutant for s-adenosyl-l-methionine production based on ethionine-resistance and sAM synthetase activity

A screening strategy of *** mutant for S-adenosyl-L-methioni...

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第八届中国酶工程学术研讨会

作者： Yi Xia Minghua Yang Jie Dou Xitao Cao Hui Wang Changlin Zhou school of life science ＆ Technology China Pharmaceutical University

s-adenosyl-l-methionine（sAM） is an important medicine and health care *** this study,we found that saccharomyces cerevisiae mutant with ethionine-resistance obtained by UV-mutagenesis showed a remarkable improvement in sAM synthetase activity（4.9 U/mg） and sAM production（6.1 g/l in a 10 l fermentor）,which were 2.7- and 3.3-fold increase compared to the wild *** suggests that ethionine-resistance screening strategy for sAM-producing *** is an effective way and potentially could be used in the production of sAM for large-scale.

关键词： UV mutagenesis Ethionine-resistanc s-adenosyl-l-methionine sAM synthetase activit saccharomyces cerevisiae

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Effect of DNA methylation on protein-DNA interaction of Hl-60 cells

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science China(life sciences) 1999年第5期42卷 501-505页

作者：何忠效白坚石张昱

Hl-60 cells have been induced with differentiation index 16% by s-adenosyl-l-methionine (sAM) as in-ducer in the presence of optimum concentration of 10 μmol/l. The methylation level of genome DNA determined by HPlC is increased during cell differentiation. When restriction endonuclease Hae Ⅲ, sma Ⅰ, sal Ⅰ, Xho Ⅰ and Hind III which are sensitive to 5-methylcytosirte were used to cleave the genome DNA, a resistance effect was found. The interaction between DNA and DNA binding proteins is changed by using gel retarding test.

关键词： s-adenosyl-l-methionine (sAM) Hl-60 cell DNA methylation protein-DNA interaction.

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