Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice.
Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice.
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DOI：
10.1053/j.gastro.2010.07.041
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发表时间：
2010-11
期刊：
影响因子：
29.4
通讯作者：
Yin XM
中科院分区：
文献类型：
--
作者：
Ding WX;Li M;Chen X;Ni HM;Lin CW;Gao W;Lu B;Stolz DB;Clemens DL;Yin XM
酗酒是造成肝损伤的主要原因。酒精性肝病的病理特征在较长时间内发展，但细胞防御机制对酒精的有害影响尚不清楚。我们研究了巨噬是否可以保护肝细胞免受乙醇毒性，巨噬是一种进化上保守的细胞机制，通常在应激反应中被激活。小鼠急性灌胃给予乙醇。体外研究了乙醇对原代肝细胞和肝细胞系的影响。乙醇诱导小鼠肝脏和培养细胞的巨噬需要乙醇代谢，产生活性氧，并抑制mTOR信号。药理药物或小干扰rna抑制巨噬可显著增加肝细胞凋亡和肝损伤；因此，巨噬保护细胞免受乙醇的毒性作用。乙醇诱导的巨噬似乎对线粒体受损和脂滴积聚的细胞有选择性，但对长寿命的蛋白质没有选择性，这可以解释其保护作用。增加巨噬在药理学上降低急性乙醇暴露相关的肝毒性和脂肪变性。大自噬保护小鼠肝脏免受乙醇诱导的毒性。修饰巨噬的试剂可能被开发为酒精性肝病患者的治疗药物。
Alcohol abuse is a major cause of liver injury. The pathologic features of alcoholic liver disease develop over prolonged periods, yet the cellular defense mechanisms against the detrimental effects of alcohol are not well understood. We investigated whether macroautophagy, an evolutionarily conserved cellular mechanism that is commonly activated in response to stress, could protect liver cells from ethanol toxicity. Mice were acutely given ethanol by gavage. The effects of ethanol on primary hepatocytes and hepatic cell lines were studied in vitro. Ethanol-induced macroautophagy in the livers of mice and cultured cells required ethanol metabolism, generated reactive oxygen species, and inhibited mTOR signaling. Suppression of macroautophagy with pharmacological agents or small interfering RNAs significantly increased hepatocyte apoptosis and liver injury; macroautophagy therefore protected cells from the toxic effects of ethanol. Macroautophagy induced by ethanol seemed to be selective for cells with damaged mitochondria and accumulated lipid droplets, but not long-lived proteins, which could account for its protective effects. Increasing macroautophagy pharmacologically reduced hepatotoxicity and steatosis associated with acute ethanol exposure. Macroautophagy protects against ethanol-induced toxicity in livers of mice. Reagents that modify macroautophagy might be developed as therapeutics for patients with alcoholic liver disease.
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影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
ATG32是一种线粒体蛋白，在线粒体过程中赋予了选择性。
影响因子：
11.8
作者：
Kanki, Tomotake;Wang, Ke;Cao, Yang;Baba, Misuzu;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
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：
15.9
作者：
Mareninova, Olga A.;Hermann, Kip;Gukovskaya, Anna S.
通讯作者：
Gukovskaya, Anna S.
影响因子：
29.4
作者：
Demeilliers, C;Maisonneuve, C;Fromenty, B
通讯作者：
Fromenty, B