The Molecular Circadian Clock and Alcohol-Induced Liver Injury.
The Molecular Circadian Clock and Alcohol-Induced Liver Injury.
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DOI：
10.3390/biom5042504
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发表时间：
2015-10-14
期刊：
影响因子：
5.5
通讯作者：
Bailey SM
中科院分区：
文献类型：
--
作者：
Udoh US;Valcin JA;Gamble KL;Bailey SM
来自实验动物研究和临床人类研究的新证据表明，昼夜节律过程、酒精使用和酒精诱导的组织损伤之间存在强烈的联系。生物钟的组成部分已被证明影响酒精的病理生理效应。相反，酒精可能会改变生物钟基因的表达，以及它们调节的有节奏的行为和代谢过程。因此，我们认为，酒精对昼夜节律的破坏可能是酒精对健康的许多不利影响的基础，酒精横跨多个器官系统。在这篇综述中，我们提供了生物钟机制的概述，并展示了酒精领域的新研究结果，这些研究表明生物钟是酒精作用和肝脏毒性的关键靶点。我们讨论了各种分子事件，酒精可能通过这些事件对肝脏的昼夜节律调节过程产生负面影响，并有助于组织病理学。阐明生物钟和酒精之间的机械联系对于开发新的预防和药物治疗酒精使用障碍和酒精介导的器官疾病将是至关重要的。
Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.