Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University , Guangzhou, China.
Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, College of Pharmacy, Jinan University , Guangzhou, China.
Biosci Biotechnol Biochem. 2020 Aug;84(8):1621-1628. doi: 10.1080/09168451.2020.1763155. Epub 2020 May 18.
A critical pathogenic factor in the development of lethal liver failure is cell death induced by the accumulation of lipid reactive oxygen species. In this study, we discovered and illuminated a new mechanism that led to alcoholic liver disease via ferroptosis, an iron-dependent regulated cell death. Study showed that both necroptosis inhibitor and ferroptosis inhibitors performed significantly protective effect on alcohol-induced cell death, while apoptosis inhibitor and autophagy inhibitor had no such effect. Our data also indicated that alcohol caused the accumulation of lipid peroxides and the mRNA expression of prostaglandin-endoperoxide synthase 2, reduced the protein expression of the specific light-chain subunit of the cystine/glutamate antiporter and glutathione peroxidase 4. Importantly, ferrostatin-1 significantly ameliorated liver injury that was induced by overdosed alcohol both and . These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment.
在致命性肝衰竭的发展中，一个关键的致病因素是脂质活性氧物质积累引起的细胞死亡。在这项研究中，我们发现并阐明了一种新的机制，即通过铁依赖性调节性细胞死亡——铁死亡，导致酒精性肝病。研究表明，坏死性凋亡抑制剂和铁死亡抑制剂对酒精诱导的细胞死亡均表现出显著的保护作用，而凋亡抑制剂和自噬抑制剂则没有这种作用。我们的数据还表明，酒精导致脂质过氧化物的积累和前列腺素内过氧化物合酶 2 的 mRNA 表达增加，胱氨酸/谷氨酸反向转运体的特异性轻链亚基和谷胱甘肽过氧化物酶 4 的蛋白表达减少。重要的是，Ferrostatin-1 显著改善了 和 中过量酒精引起的肝损伤。这些发现强调，靶向铁死亡可能成为治疗酒精性肝病的一种肝脏保护策略。
