TRPM2 Mediates Hepatic Ischemia-Reperfusion Injury via Ca²⁺-Induced Mitochondrial Lipid Peroxidation through Increasing ALOX12 Expression.

ABSTRACT: Hepatic ischemia-reperfusion (IR) injury is a serious clinical problem that complicates liver resection and transplantation. Despite recent advances in understanding of the pathophysiology of hepatic IR injury, effective interventions and therapeutics are still lacking. Here, we examined the role of transient receptor potential melastatin 2 (TRPM2), a Ca²⁺-permeable, non-selective cation channel, in mediating hepatic IR injury. Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction, inflammation, and cell death in mice. Moreover, RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways. Consistently, as a ferroptosis inducer, (1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 in

SUBMITTER: Zhong C 

PROVIDER: S-EPMC10232356 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature