自噬
帕金
粒体自噬
脂肪肝
化学
对乙酰氨基酚
脂肪性肝炎
内分泌学
小干扰RNA
小窝蛋白1
转染
内科学
脂滴
细胞凋亡
生物
脂肪变性
生物化学
医学
基因
疾病
帕金森病
作者
Wei Jiang,Jiarong Wang,Weiju Xue,Xin Jiao,Congjian Shi,Jiagen Wen,Xiaowen Feng,Yan Huang,Chengmu Hu
标识
DOI:10.1016/j.ejphar.2021.174324
摘要
Alcoholic fatty liver (AFL) is a disease characterized by the abnormal structure and dysfunction of hepatocytes caused by long-term, excessive drinking. Acetaminophen (APAP) is a commonly used painkiller, but it can aggravate lipid deposition in the liver and cause liver injury when used in fatty liver disease. Here, we investigated the effect of caveolin-1 (CAV-1), an intracellular stent protein, on the pathogenesis of APAP aggravated lipid deposition in AFL mice. This study shows that lipid accumulation was more severe in APAP groups than in alcohol-treated mice. The CAV-1 stent-like domain (CSD, 82-101 amino acids of caveolin-1), used to upregulate CAV-1 expression, could reduce lipid accumulation and activate autophagy in AFL mice treated with APAP. The levels of CAV-1 and autophagy-related proteins (LC3-II/I and Beclin-1) had decreased, whereas SREBP-1c had increased in A/O (alcohol and oleic acid) and APAP-co-treated L02 cells. CAV-1 small interfering RNA and CAV1-overexpressing plasmid were separately transfected into A/O and APAP co-treated L02 cells. When CAV-1 was downregulated, the levels of Pink-1, Parkin, and autophagy-related proteins (LC3-II/I and Beclin-1) were decreased, whereas SREBP-1c was increased. The opposite trend was observed when CAV-1 was overexpressed. The results show that CAV-1 reduced lipid accumulation in L02 cells and activated Pink-1/Parkin-related mitophagy. This study highlights the positive role of CAV-1 in APAP-increased lipid accumulation under the AFL status and provides a new understanding of the function of CAV-1 in the liver through mitophagy associated with the Pink-1/Parkin pathway.
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