坏死性下垂
裂谷1
自噬
程序性细胞死亡
细胞生物学
化学
自噬体
激酶
时尚
蛋白激酶A
癌症研究
生物
细胞凋亡
生物化学
半胱氨酸蛋白酶
作者
Yuelin Chen,Meitong Liu,Hongdi Wei,Jianxia Guo,Shengzhuo Zhang,Xiujuan Bu,Shanshan Chen,Duoduo Zhang,Shuang Guan
标识
DOI:10.1016/j.fct.2023.114124
摘要
Excessive alcohol consumption leads to serious liver injury. Necroptosis is a programmed cell death form, which has been confirmed to be involved in alcoholic liver injury. However, the exact mechanism remains still unclear. In this study, we found that ethanol caused hepatocytes necroptosis by activating receptor-interacting serine/threonine-protein kinase 1 and 3 (RIPK1 and RIPK3). Meanwhile, autophagy was activated in ethanol-treated hepatocytes. Accumulative studies have demonstrated a possible link between autophagy and necroptosis. Microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker protein, is essential for autophagosome biogenesis/maturation. But little attention has been paid to its functional role. In this study, we explored whether LC3 was involved in ethanol-induced necroptosis. The data showed that LC3 interacted with RIPK1 and RIPK3 in ethanol-treated AML12 cells and mice liver by co-immunoprecipitation (co-IP) and colocalization assay. Ethanol-induced necrosome formation and subsequent necroptosis were alleviated in hepatocytes by knockdown of LC3 or autophagy inhibitor 3-methyladenine (3-MA). These results demonstrated that LC3 accumulation facilitated the formation of necrosome by LC3-RIPK1 and LC3-RIPK3 interactions, eventually caused hepatocytes necroptosis after acute ethanol exposure. Our current research could potentially offer a new understanding of the intricate mechanisms involved in the development of acute alcoholic liver injury.
科研通智能强力驱动
Strongly Powered by AbleSci AI