Ferroptosis is involved in alcohol-induced cell death in vivo and in vitro |
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| Authors: | Chun-Yu Liu Min Wang Hong-Min Yu Fang-Xuan Han Qiong-Shi Wu Xing-Jun Cai |
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| Institution: | 1. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University , Guangzhou, China;2. Guangdong Engineering Research Center of Chinese Medicine &3. Disease Susceptibility, College of Pharmacy, Jinan University , Guangzhou, China;4. Department of Pharmacy, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) , Haikou, China;5. Department of Respiratory and Critical Care Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University) , Haikou, China |
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| Abstract: | ABSTRACT 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 in vitro 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 in vitro and in vivo. These findings highlight that targeting ferroptosis serves as a hepatoprotective strategy for alcoholic liver disease treatment. |
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| Keywords: | Alcohol hepatotoxicity ferroptosis lipid peroxidation |
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