Pim-1 kinase protects the liver from ischemia reperfusion injury by regulating dynamics-related protein 1

• Published in: iScience Vol. 27; no. 7; p. 110280
• Main Authors: Sun, Yan-dong, Xu, Qing-guo, Dai, De-shu, Wang, Shu-xian, Li, Xin-qiang, Shi, Shang-heng, Jiang, Peng, Jin, Yan, Wang, Xin, Zhang, Yong, Wang, Feng, Liu, Peng, Zhang, Bing-liang, Li, Tian-xiang, Xu, Chuan-shen, Wu, Bin, Cai, Jin-zhen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.07.2024; Elsevier
• Subjects: Cellular physiology; Endocrinology; Cellular physiology; Endocrinology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.110280

Hepatic ischemia-reperfusion (IR) injury significantly impacts liver transplantation success, yet current treatments remain inadequate. This study explores the role of Proto-oncogene serine/threonine-protein kinase (Pim-1) in liver IR, an area previously unexplored. Utilizing a mouse liver IR in vivo model and a MIHA cell hypoxia–reoxygenation in vitro model, we observed that Pim-1 expression increases following IR, inversely correlating with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Increased Pim-1 expression stabilizes mitochondrial membranes by modifying Drp1 phosphorylation, reducing mitochondrial fission and apoptosis, thereby mitigating liver damage. Additionally, we discovered that elevated Pim-1 expression is dependent on the trimethylation of histone H3 lysine 9 during liver IR. These findings underscore the importance and potential clinical application of targeting Pim-1 in treating hepatic IR, presenting a novel therapeutic avenue. [Display omitted] •Pim-1 levels increase post-reoxygenation in MIHA cells•High Pim-1 correlates with better liver transplant recovery•Pim-1 inhibition raises necrosis in liver IR models•Pim-1 regulates Drp1, protecting mitochondrial integrity Endocrinology; Cellular physiology