AMP-activated protein kinase protects against necroptosis via regulation of Keap1-PGAM5 complex.

ABSTRACT: BACKGROUND:The AMP-activated protein kinase (AMPK) plays critical roles in growth regulation and metabolism reprogramming. AMPK activation protects cells against apoptosis from injury in different cell and animal models. However, its function in necroptosis remains largely unclear. METHODS AND RESULTS:In the current study, we demonstrated that AMPK was activated upon necroptosis induction and protected mouse embryonic fibroblasts (MEFs) and cardiomyocytes from N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and reactive oxygen species (ROS) induced necroptosis. Activation of AMPK with chemicals A-769662, 2-deoxyglucose (2-DG), and metformin or constitutively active (CA) AMPK markedly decreased necroptosis and cytotoxicity induced by MNNG. In contrast, AMPK inhibitor compound C, dominant negati

SUBMITTER: Wang YS 

PROVIDER: S-EPMC5873603 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature