Ameliorative Effect of Luteolin on H2O2-Induced Mitophagy and Apoptosis in Cardiomyocytes Through Modulation of the AMPK/mTOR Pathway

BACKGROUND: )-induced mitophagy and apoptosis in cardiomyocytes. METHODS: ) (ATG5), microtubule-associated protein 1 light chain 3 beta (LC3B), B-cell lymphoma 2 (BCL2)-associated X protein (Bax), B-cell leukemia/lymphoma 2 (Bcl-2), PTEN-induced putative kinase 1 (PINK1), and peroxisome proliferator-activated receptor gamma (PPARγ) was analyzed by Western blotting. Intracellular reactive oxygen species (ROS) levels were assessed using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining (DCFH) oxidation staining. The expressions of phosphorylated AMP-activated protein kinase alpha (p-AMPKα), SIRT1, and caspase 8 were evaluated by immunofluorescence. Mitochondrial membrane potential and mitochondrial permeability transition pore (MPTP) opening were assessed using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine iodide (JC-1) staining and an MPTP assay kit, respectively. RESULTS: -induced upregulation of proteins associated with the AMPK/mTOR signaling axis, mitophagy, and apoptosis. CONCLUSIONS: These findings suggest that luteolin protects H9c2 cells from mitochondria-mediated apoptosis by modulating the AMPK/mTOR signaling pathway and inhibiting excessive mitophagy. Moreover, these results suggest that luteolin has potential as a therapeutic agent for preventing and treating cardiovascular diseases.