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

被引:0
|
作者
Sun, Yan-dong [1 ]
Xu, Qing-guo [1 ]
Dai, De-shu [1 ]
Wang, Shu-xian [1 ]
Li, Xin-qiang [1 ]
Shi, Shang-heng [1 ]
Jiang, Peng [1 ]
Jin, Yan [1 ]
Wang, Xin [1 ]
Zhang, Yong [1 ]
Wang, Feng [1 ]
Liu, Peng [1 ]
Zhang, Bing-liang [1 ]
Li, Tian-xiang [1 ]
Xu, Chuan-shen [1 ]
Wu, Bin [1 ]
Cai, Jin-zhen [1 ]
机构
[1] Qingdao Univ, Affiliated Hosp, Inst Transplantat Sci, Organ Transplantat Ctr, Qingdao, Shandong, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
MITOCHONDRIAL FISSION; MECHANISMS; PHOSPHORYLATION; INTEGRITY; WARM; DRP1;
D O I
10.1016/j.isci.2024.110280
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:18
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