Department of Pharmacology, School of Pharmacy, Nantong University, Key Laboratory of Inflammation and Molecular Drug Target of Jiangsu Province, Nantong, Jiangsu, China.
J Biochem Mol Toxicol. 2019 Feb;33(2):e22249. doi: 10.1002/jbt.22249. Epub 2018 Oct 28.
Sirtuin3 (SIRT3) plays an important role in maintaining normal mitochondrial function and alleviating oxidative stress. After carbon tetrachloride (CCl ) administration, the expression of SIRT3 decreased in the liver of mice, which indicated that the SIRT3 might play a crucial role during chemical-induced acute hepatic injury. To verify the hypothesis, CCl was given to induce acute hepatic injury in SIRT3 knockout (KO) mice and wild-type (WT) mice. CCl -induced liver injury was more severe in SIRT3 KO mice compared with the WT mice. In addition, the oxidative stress induced by CCl was enhanced in the SIRT3 KO mice. Furthermore, the increased expression of dynamin-related protein 1 was also aggravated in SIRT3 KO mice after CCl administration. In conclusion, our study demonstrated that SIRT3 deficiency exacerbated CCl -induced impairment of the liver in mice, and the mechanism might be related to enhanced oxidative stress.
Sirtuin3(SIRT3)在维持正常线粒体功能和减轻氧化应激方面发挥着重要作用。四氯化碳(CCl4)给药后,小鼠肝脏中 SIRT3 的表达下降,这表明 SIRT3 在化学诱导的急性肝损伤中可能发挥关键作用。为了验证这一假设,用 CCl4 诱导 SIRT3 敲除(KO)小鼠和野生型(WT)小鼠发生急性肝损伤。与 WT 小鼠相比,SIRT3 KO 小鼠的 CCl4 诱导的肝损伤更严重。此外,SIRT3 KO 小鼠的氧化应激也增强。此外,在给予 CCl4 后,SIRT3 KO 小鼠中 dynamin-related protein 1 的表达增加也加剧。总之,我们的研究表明,SIRT3 缺乏加剧了 CCl4 诱导的小鼠肝损伤,其机制可能与增强的氧化应激有关。