The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.
The Altered Hepatic Tubulin Code in Alcoholic Liver Disease.
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DOI：
10.3390/biom5032140
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发表时间：
2015-09-18
期刊：
影响因子：
5.5
通讯作者：
Tuma PL
中科院分区：
文献类型：
--
作者：
Groebner JL;Tuma PL
导致酒精性肝病进展的分子机制几十年来一直被积极研究。由于肝微管细胞骨架支持无数的细胞过程，因此一直是许多此类机制研究的焦点。长期以来，人们一直认为α-微管蛋白是高活性乙醇代谢产物和活性氧类修饰的主要靶点。现在也很明显，酒精暴露会诱导翻译后修饰，这是自然过程的一部分，主要是乙酰化。本文对微管蛋白密码子的修饰以及乙醇代谢物的加合物进行了综述。描述了微管修饰的潜在细胞后果，重点介绍了酒精引起的蛋白质运输缺陷和强化的脂肪变性。可能的机制可以解释肝功能障碍被描述，并如何与肝损伤的发生进行了讨论。最后，我们认为改变细胞乙酰化状态的药物可能代表着治疗肝病的一种新的治疗策略。
The molecular mechanisms that lead to the progression of alcoholic liver disease have been actively examined for decades. Because the hepatic microtubule cytoskeleton supports innumerable cellular processes, it has been the focus of many such mechanistic studies. It has long been appreciated that α-tubulin is a major target for modification by highly reactive ethanol metabolites and reactive oxygen species. It is also now apparent that alcohol exposure induces post-translational modifications that are part of the natural repertoire, mainly acetylation. In this review, the modifications of the “tubulin code” are described as well as those adducts by ethanol metabolites. The potential cellular consequences of microtubule modification are described with a focus on alcohol-induced defects in protein trafficking and enhanced steatosis. Possible mechanisms that can explain hepatic dysfunction are described and how this relates to the onset of liver injury is discussed. Finally, we propose that agents that alter the cellular acetylation state may represent a novel therapeutic strategy for treating liver disease.