George Akash K, Behera Jyotirmaya, Kelly Kimberly E, Zhai Yuankun, Tyagi Neetu
Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Department of Physiology, School of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Brain Res Bull. 2017 Apr;130:251-256. doi: 10.1016/j.brainresbull.2017.02.002. Epub 2017 Feb 14.
Alcohol is one of the most socially accepted addictive drugs in modern society. Its abuse affects virtually all organ systems with the central nervous system (CNS) being particularly vulnerable to excessive alcohol exposure. Alcohol exposure also causes profound damage to both the adult and developing brain. Excessive alcohol consumption induces numerous pathophysiological stress responses, one of which is the endoplasmic reticulum (ER) stress response. Potential mechanisms that trigger the alcohol induced ER stress response are either directly or indirectly related to alcohol metabolism, which include toxic levels of acetaldehyde and homocysteine, oxidative stress and abnormal epigenetic modifications. Growing evidence suggests that HS is the most recently recognized gasotransmitter with tremendous physiological protective functions against oxidative stress induced neurotoxicity. In this review we address the alcohol induced oxidative stress mediated ER stress and the role of HS in its mitigation in the context of alcohol neurotoxicity. Interruption of ER stress triggers is anticipated to have therapeutic benefits for alcohol mediated diseases and disorders.
酒精是现代社会中最被社会所接受的成瘾性药物之一。其滥用几乎会影响所有器官系统，其中中枢神经系统（CNS）特别容易受到过量酒精暴露的影响。酒精暴露还会对成人大脑和发育中的大脑造成严重损害。过量饮酒会引发众多病理生理应激反应，其中之一是内质网（ER）应激反应。触发酒精诱导的内质网应激反应的潜在机制与酒精代谢直接或间接相关，包括乙醛和同型半胱氨酸的毒性水平、氧化应激和异常的表观遗传修饰。越来越多的证据表明，硫化氢（HS）是最近被认可的气体信号分子，对氧化应激诱导的神经毒性具有巨大的生理保护作用。在本综述中，我们探讨了酒精诱导的氧化应激介导的内质网应激以及硫化氢在酒精神经毒性背景下减轻内质网应激中的作用。预计内质网应激触发因素的中断对酒精介导的疾病和紊乱具有治疗益处。
