Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity.
Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity.
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DOI：
10.1016/j.redox.2014.10.006
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发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Thomes, Paul G.
中科院分区：
文献类型：
--
作者：
Donohue, Terrence M., Jr.;Thomes, Paul G.
在这篇综述中，我们描述了关于酒精暴露对肝细胞中两个主要分解代谢系统影响的研究结果：泛素-蛋白酶体系统（UPS）和自噬。这些水解系统并不是肝细胞所独有的。它们存在于所有真核组织和细胞中。然而，由于肝脏是乙醇代谢的主要场所，因此大量饮酒对肝脏的损害最大。因此，本综述的重点是具体描述乙醇氧化如何调节 UPS 和自噬的活性，以及这些变化导致酒精性肝损伤发病机制的机制。在这里，我们描述了细胞水解系统的历史和重要性，然后描述了每个分解代谢途径以及乙醇暴露对每个分解代谢途径的差异调节。总体而言，这些分解代谢系统参与酒精性肝病发病机制的证据非常充分。它强调了它们的重要性，不仅作为细胞回收和最终能量产生的有效手段，而且作为细胞防御的重要组成部分。活跃的细胞内分解代谢系统对于细胞存活至关重要。自噬和泛素-蛋白酶体系统（UPS）是主要的分解代谢系统。酒精氧化成乙醛可调节肝脏中的自噬和 UPS。连续（慢性）乙醇氧化会破坏肝自噬和 UPS。这种破坏会导致酒精性肝损伤。
In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin–proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, we describe the history and the importance of cellular hydrolytic systems, followed by a description of each catabolic pathway and the differential modulation of each by ethanol exposure. Overall, the evidence for an involvement of these catabolic systems in the pathogenesis of alcoholic liver disease is quite strong. It underscores their importance, not only as effective means of cellular recycling and eventual energy generation, but also as essential components of cellular defense. Active intracellular catabolic systems are crucial to cell survival. Autophagy and the ubiquitin–proteasome system (UPS) are predominant catabolic systems. Alcohol oxidation to acetaldehyde modulates autophagy and the UPS in liver. Continuous (chronic) ethanol oxidation disrupts hepatic autophagy and the UPS. Such disruption contributes to alcoholic liver injury.
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影响因子：
4.1
作者：
DOHERTY, FJ;OSBORN, NU;MAYER, RJ
通讯作者：
MAYER, RJ
DOI：
10.1111/j.1530-0277.2012.01742.x
发表时间：
2012-08
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Dolganiuc A;Thomes PG;Ding WX;Lemasters JJ;Donohue TM Jr
通讯作者：
Donohue TM Jr
影响因子：
11.4
作者：
Cascio, P;Hilton, C;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
13.3
作者：
Chen, Gang;Ke, Zunji;Luo, Jia
通讯作者：
Luo, Jia
影响因子：
56.9
作者：
BACHMAIR, A;FINLEY, D;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A