氧化应激
HDAC6型
对乙酰氨基酚
谷胱甘肽
肝损伤
化学
药理学
乙酰化
细胞凋亡
下调和上调
组蛋白脱乙酰基酶
生物化学
组蛋白
医学
酶
基因
作者
Guodong Zhang,Lili Wang,Ling Zheng,Shiqi Wang,Rong-quan Yang,Yuting He,Junwei Wang,Mingyu Zhao,Yi Ding,Mei L,Tianyu Yang,Baoming Wu,Hao Cui,Lei Zhang
标识
DOI:10.1016/j.intimp.2024.111861
摘要
Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.
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