Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Original Article
AMPK-mTOR-ULK1-mediated autophagy protects carbon tetrachloride-induced acute hepatic failure by inhibiting p21 in rats
Qiwen WangWeixia LiuGaopeng LiuPan LiXueqiang GuoChunyan Zhang
著者情報
ジャーナル オープンアクセス

2021 年 34 巻 1 号 p. 73-82

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抄録

Autophagy is a lysosomal-dependent degradation pathway in eukaryotic cells. Recent studies have reported that autophagy can facilitate the activation of hepatic stellate cells (HSCs) and fibrogenesis of the liver during long-term carbon tetrachloride (CCl4) exposure. However, little is known about the role of autophagy in CCl4-induced acute hepatic failure (AHF). This study aimed to identify whether modulation of autophagy can affect CCl4-induced AHF and evaluate the upstream signaling pathways mediated by CCl4-induced autophagy in rats. The accumulation of specific punctate distribution of endogenous LC3-II, increased expression of LC3-II, Atg5, and Atg7 genes/proteins, and decreased expression of p62 gene were observed after acute liver injury was induced by CCl4 in rats, indicating that CCl4 resulted in a high level of autophagy. Moreover, loss of autophagic function by using chloroquine (CQ, an autophagic inhibitor) aggravated liver function, leading to increased expression of p21 (a cyclin-dependent kinase inhibitor) in CCl4-treated rats. Furthermore, the AMPK-mTORC1-ULK1 axis was found to serve a function in CCl4-induced autophagy. These results reveal that AMPK-mTORC1-ULK1 signaling-induced autophagy has a protective role in CCl4-induced hepatotoxicity by inhibiting the p21 pathway. This study suggests a useful strategy aimed at ameliorating CCl4-induced acute hepatotoxicity by autophagy.

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© 2021 The Japanese Society of Toxicologic Pathology
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