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首页> 外文期刊>International Journal of Hepatology >New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
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New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

机译：酒精诱导的内质网应激和肝病发病机理的新见解

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Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.
机译：酒精引起的肝病越来越多地导致全世界人类的死亡。近年来，酒精诱导的内质网应激和细胞蛋白质稳态的破坏已被认为是导致肝脏疾病的重要机制。酒精诱导的内质网应激不仅发生在培养的肝细胞中，而且还体内发生在包括小鼠，大鼠，小型猪，斑马鱼和人类在内的几种物种的肝脏中。已确定的内质网应激的原因包括乙醛，氧化应激，一种碳代谢受损，有毒脂质种类，胰岛素抵抗，钙稳态失调和表观遗传修饰异常。酒精引起的肝损伤中每种原因的重要性取决于酒精的剂量，持续时间和暴露方式，遗传因素，环境因素，与其他病原性途径的串扰以及肝病的阶段。饮酒期间ER应力或多或少会一直发生，这会干扰肝蛋白的稳态，增殖和细胞周期进程，从而促进晚期肝病的发展。越来越多的证据表明，长期饮酒和内质网应激可能直接参与肝细胞癌变（HCC）。解剖导致肿瘤发生的内质网应激信号通路将揭示潜在的治疗靶点，用于干预和治疗人类酒精中毒与肝癌。

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