Department of Pathology, Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
Exp Mol Pathol. 2010 Jun;88(3):380-7. doi: 10.1016/j.yexmp.2010.03.004. Epub 2010 Mar 17.
S-adenosylmethionine (SAMe), the major methyl donor for DNA and histone methylation was fed with ethanol for 1month in order to modify the effects of ethanol on rat liver. The following parameters were studied to determine the effects of SAMe; liver histology, the blood alcohol cycle (BAL), changes in gene expression mined from microarray analysis, changes in histone methylation, changes in liver SAMe levels and its metabolites and ADH. SAMe changed the type of fatty liver, reduced liver ALT levels and prevented the BAL cycle caused by intragastric ethanol feeding. Microarray analysis showed that SAMe feeding prevented most of the changes in gene expression induced by ethanol feeding, presumably by inducing H3K27me3 and gene silencing. H3K27me3 was significantly increased by SAMe with or without ethanol feeding. It is concluded that SAMe feeding stabilized global gene expression so that the changes in gene expression involved in the blood alcohol cycle were prevented.
S-腺苷甲硫氨酸(SAMe)是 DNA 和组蛋白甲基化的主要甲基供体,用乙醇喂养 1 个月,以改变乙醇对大鼠肝脏的影响。研究了以下参数来确定 SAMe 的作用:肝组织学、血液酒精循环(BAL)、从微阵列分析中挖掘的基因表达变化、组蛋白甲基化变化、肝 SAMe 水平及其代谢物和 ADH 的变化。SAMe 改变了脂肪肝的类型,降低了 ALT 水平,并防止了因胃内乙醇喂养引起的 BAL 循环。微阵列分析表明,SAMe 喂养防止了乙醇喂养引起的大多数基因表达变化,可能是通过诱导 H3K27me3 和基因沉默。SAMe 喂养或不喂养都会显著增加 H3K27me3。结论是,SAMe 喂养稳定了全局基因表达,从而防止了血液酒精循环中涉及的基因表达变化。