Dietary L-methionine supplementation mitigates gamma-radiation induced global DNA hypomethylation: Enhanced metabolic flux towards S-adenosyl-L-methionine (SAM) biosynthesis increases genomic methylation potential
Dietary L-methionine supplementation mitigates gamma-radiation induced global DNA hypomethylation: Enhanced metabolic flux towards S-adenosyl-L-methionine (SAM) biosynthesis increases genomic methylation potential
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DOI：
10.1016/j.fct.2014.03.040
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发表时间：
2014-07-01
影响因子：
4.3
通讯作者：
Verma, Poonam
中科院分区：
文献类型：
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作者：
Batra, Vipen;Verma, Poonam
本研究的目的是检查Co-60-γ（γ）辐射对维持（6周）正常对照饮食（NCD）和L-蛋氨酸补充饮食（MSD）的小鼠的基因组DNA甲基化（如果有的话）的调节的影响。为了阐明可能的潜在机制，我们将动物暴露于γ辐射（2、3和4戈伊），并研究了参与S-腺苷-L-甲硫氨酸（SAM）生成的下游代谢产物和酶的谱。还对肝脏样本进行了组织病理学检查。与NCD喂养和辐照动物相比，肝脏叶酸、胆碱和L-蛋氨酸水平中度降低，而MSD喂养和辐照动物的肝脏SAM水平升高。在这些条件下，甲硫氨酸腺苷转移酶（MAT）和L-甲硫氨酸合酶（MSase）的活动的显着调制进行了观察。伴随着肝脏SAM池的增加，MSD喂养小鼠中DNA甲基转移酶（dnmt）活性的增加表明朝向DNA甲基化的代谢通量增强。进一步的结果表明，与NCD喂养和辐照的动物相比，MSD喂养和辐照的小鼠的基因组DNA甲基化和5-甲基-2 '-脱氧胞苷残基保持在正常水平。总之，我们的研究结果表明，通过饮食中补充L-蛋氨酸，增加预先形成的甲基基团的供应可能会显着增加辐射应激损害DNA甲基化循环的甲基化潜力。(C)2014爱思唯尔有限公司版权所有。
The objective of this study was to examine the effect of Co-60-gamma (gamma) radiation on modulation of genomic DNA methylation, if any, of mice maintained (6 weeks) on normal control diet (NCD) and L-methionine supplemented diet (MSD). To elucidate the possible underlying mechanism(s), we exposed the animals to gamma-radiation (2, 3 and 4 Gy) and investigated the profile of downstream metabolites and enzymes involved in S-adenosyl-L-methionine (SAM) generation. Liver samples were also subjected to histopathological examinations. Compared to NCD fed and irradiated animals, hepatic folate, choline and L-methionine levels decreased moderately, while hepatic SAM levels increased in MSD fed and irradiated animals. Under these conditions, a marked modulation of methionine adenosyltransferase (MAT) and L-methionine synthase (MSase) activities was observed. Concomitant with increase in liver SAM pool, increased DNA methyltransferase (dnmt) activity in MSD fed mice indicated enhanced metabolic flux towards DNA methylation. Further results showed that genomic DNA methylation and 5-methyl-2'-deoxy cytidine residues were maintained at normal levels in MSD fed and irradiated mice compared to NCD fed and irradiated animals. In conclusion, our results suggest that increasing supply of preformed methyl groups, via dietary L-methionine supplementation might significantly increase methylation potential of radiation stress compromised DNA methylation cycle. (C) 2014 Elsevier Ltd. All rights reserved.