Induction of CYP2E1 in non-alcoholic fatty liver diseases.
Induction of CYP2E1 in non-alcoholic fatty liver diseases.
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在非酒精性脂肪肝疾病中诱导CYP2E1。
DOI：
10.1016/j.yexmp.2015.11.008
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发表时间：
2015-12
影响因子：
3.6
通讯作者：
Zhu L
中科院分区：
文献类型：
--
作者：
Aljomah G;Baker SS;Liu W;Kozielski R;Oluwole J;Lupu B;Baker RD;Zhu L
越来越多的证据支持内源性酒精代谢在非酒精性脂肪性肝炎(NASH)发病机制中的作用。然而，目前尚不清楚单纯性脂肪变性的肝脏中酒精代谢基因的表达是否发生了变化。目前还存在关于脂肪酸是否会导致脂肪肝中的CYP2E1的争论。本研究用实时定量聚合酶链式反应(qRT-PCR)检测了单纯性脂肪变性患者肝组织中酒精代谢基因的表达，并与Nash肝组织和正常对照进行了比较。用qRT-PCR和Western blotts检测乙醇或油酸对培养的HepG2细胞酒精代谢基因的诱导作用。我们发现酒精代谢基因ADH1C、ADH4、ADH6、过氧化氢酶和CYP2E1mRNA在单纯性脂肪变性的肝脏中表达升高，与在Nash肝脏中的表达水平相似。在培养的HepG2细胞中，乙醇可诱导细胞色素P450 2E1mRNA和蛋白的表达，但不能诱导ADH4或ADH6的表达；油酸不能诱导这些基因的表达。这些结果提示，酒精代谢升高可能参与了NAFLD在单纯性脂肪变性阶段和更严重阶段的发病机制。我们的体外实验数据支持内源性酒精而不是脂肪酸诱导的细胞色素P450-2E1的表达。
Mounting evidence supports a contribution of endogenous alcohol metabolism in the pathogenesis of non-alcoholic steatohepatitis (NASH). However, it is not known whether the expression of alcohol metabolism genes is altered in the livers of simple steatosis. There is also a current debate on whether fatty acids induce CYP2E1 in fatty livers. In this study, expression of alcohol metabolizing genes in the liver biopsies of simple steatosis patients was examined by quantitative real-time PCR (qRT-PCR), in comparison to biopsies of NASH livers and normal controls. Induction of alcohol metabolizing genes was also examined in cultured HepG2 cells treated with ethanol or oleic acid, by qRT-PCR and Western blots. We found that the mRNA expression of alcohol metabolizing genes including ADH1C, ADH4, ADH6, catalase and CYP2E1 were elevated in the livers of simple steatosis, to similar levels found in NASH livers. In cultured HepG2 cells, ethanol induced the expression of CYP2E1 mRNA and protein, but not ADH4 or ADH6; oleic acid did not induce any of these genes. These results suggest that elevated alcohol metabolism may contribute to the pathogenesis of NAFLD at the stage of simple steatosis as well as more severe stages. Our in vitro data support that CYP2E1 is induced by endogenous alcohol but not by fatty acids.