کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1908592 1046672 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cytochrome P4502E1, oxidative stress, JNK, and autophagy in acute alcohol-induced fatty liver
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Cytochrome P4502E1, oxidative stress, JNK, and autophagy in acute alcohol-induced fatty liver
چکیده انگلیسی

Binge alcohol drinking induces hepatic steatosis. Recent studies showed that chronic ethanol-induced fatty liver was, at least in part, CYP2E1 dependent. The mechanism of acute alcohol-induced steatosis and whether CYP2E1 plays any role are still unclear. Increasing oxidative stress by alcohol can activate the JNK MAP kinase signaling pathway, suggesting that JNK might be a target for prevention of alcohol-induced steatosis. We used CYP2E1 knockout (KO) mice, a JNK inhibitor, and JNK1 or JNK2 knockout mice to test the role of CYP2E1, JNK, and the individual role of JNK1 and JNK2 in acute alcohol-induced steatosis. In wild-type (WT) mice, acute alcohol activates CYP2E1 and increases oxidative stress, which reciprocally increases activation of the JNK signaling pathway. Acute alcohol-induced fatty liver and oxidative stress were blunted in CYP2E1 KO mice and by the JNK inhibitor in WT mice. The antioxidant N-acetylcysteine decreased the acute alcohol-induced oxidative stress, the activation of JNK, and the steatosis but not the activation of CYP2E1. Acute alcohol decreased autophagy and increased expression of SREBP, effects blocked by the JNK inhibitor. Acute alcohol-induced fatty liver was the same in JNK1 and JNK2 KO mice as in WT mice; thus either JNK1 or JNK2 per se is sufficient for induction of steatosis by acute alcohol. The results show that acute alcohol elevation of CYP2E1, oxidative stress, and activation of JNK interact to lower autophagy and increase lipogenic SREBP resulting in fatty liver.


► Acute alcohol induces hepatic lipid accumulation via a CYP2E1-dependent reaction.
► Activation of JNK is necessary for the acute alcohol-induced steatosis.
► CYP2E1-derived oxidant stress plays a key role in the lipid accumulation and the activation of JNK.
► A decrease in autophagy is associated with the alcohol-induced steatosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 53, Issue 5, 1 September 2012, Pages 1170–1180
نویسندگان
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