CYP2E1 enhances ethanol-induced lipid accumulation but impairs autophagy in HepG2 E47 cells.
CYP2E1 enhances ethanol-induced lipid accumulation but impairs autophagy in HepG2 E47 cells.
复制标题
DOI：
10.1016/j.bbrc.2010.09.127
复制
发表时间：
2010-11-05
影响因子：
3.1
通讯作者：
Cederbaum A
中科院分区：
文献类型：
--
作者：
Wu D;Wang X;Zhou R;Cederbaum A
自噬和脂代谢的调节和功能最近被报道是相互关联的。巨自噬调节储存在脂滴中的脂类的分解。抑制自噬会导致脂肪肝的发展。我们在体外评价了细胞色素P450 2 1调节乙醇对脂质堆积和自噬的影响的能力。用50、100和150 mM的乙醇处理表达细胞色素P450-2的E47-HepG2细胞4~5天。乙醇诱导E47细胞的脂质堆积和甘油三酯(TG)增加的程度比不表达CYP2E1的对照C34细胞更大。相反，乙醇对C34细胞的自噬(Lc3 II/Lc3 I比值)的诱导作用明显强于E47细胞。乙醇处理后，E47细胞中P62蛋白表达明显增强。因此，乙醇对脂类堆积的影响与细胞自噬之间存在相互作用关系。3-甲基腺嘌呤(3MA)抑制自噬，使自噬增强的C34细胞中的脂质积累和TG水平增加，而对自噬较低的E47细胞中的脂质积累和TG水平的促进作用较小。乙醇诱导E47细胞和C34细胞的CYP2E1活性和氧化应激。这些实验表明，CYP2E1的表达可能会损害自噬的形成，自噬的形成有助于肝脏中的脂肪积累。我们推测，CYP2E1诱导的氧化应激促进了乙醇对脂滴的积累，这可能是抑制肝脏自噬的原因。
The regulation and function of autophagy and lipid metabolism have recently been reported to be reciprocally related. Macroautophagy mediates the breakdown of lipids stored in lipid droplets. An inhibition of autophagy leads to the development of a fatty liver. We evaluated the ability of CYP2E1 to modulate the effects of ethanol on lipid accumulation and autophagy in vitro. The E47 HepG2 cell which expresses CYP2E1 was treated with ethanol at 50, 100 and 150 mM for 4 or 5 days. Ethanol induced lipid accumulation and an increase of triglycerides (TG) in E47 cells to a greater extent than in control C34 cells which do not express CYP2E1. In contrast, autophagy (LC3 II/LC3 I ratio) was significantly induced by ethanol in C34 cells to a greater extent than in E47 cells. P62 was significantly increased in E47 cells after ethanol treatment. Thus, there is a reciprocal relationship between the effects of ethanol on lipid accumulation and autophagy in the CYP2E1-expressing cells. Inhibition of autophagy by 3-methyladenine (3MA), increased lipid accumulation and TG levels in C34 cells which display elevated autophagy, but enhanced lipid accumulation and TG level to a lesser extent in E47 cells which displayed lower autophagy. Ethanol induced CYP2E1 activity and oxidative stress in E47 cells compared with C34 cells. These experiments suggest that the expression of CYP2E1 may impair autophagy formation which contributes to lipid accumulation in the liver. We hypothesize that CYP2E1-induced oxidative stress promotes the accumulation of lipid droplets by ethanol and this may be responsible for the suppression of autophagy in the liver.
登录
查看更多内容
影响因子：
13.5
作者：
Lu, Yongke;Zhuge, Jian;Cederbaum, Arthur I.
通讯作者：
Cederbaum, Arthur I.
影响因子：
64.8
作者：
Singh, Rajat;Kaushik, Susmita;Wang, Yongjun;Xiang, Youqing;Novak, Inna;Komatsu, Masaaki;Tanaka, Keiji;Cuervo, Ana Maria;Czaja, Mark J.
通讯作者：
Czaja, Mark J.
影响因子：
1.9
作者：
Lu, Yuan;Li, Ying;Zheng, Ronger
通讯作者：
Zheng, Ronger
DOI：
10.1152/ajpgi.00406.2005
发表时间：
2006-04-01
影响因子：
4.5
作者：
Wu, DF;Cederbaum, AI
通讯作者：
Cederbaum, AI
影响因子：
2.3
作者：
Lieber, CS
通讯作者：
Lieber, CS