Does α-Ketoglutarate improve cardiac insufficiency and alleviate cardiomyocyte damage in pressure overload-induced mice and AngII-treated cardiomyocytes?
α-Ketoglutarate alleviates cardiomyocyte damage and improves cardiac insufficiency by promoting mitophagy and inhibiting ferroptosis via the NAD+-SIRT1 signaling pathway.
BACKGROUND: levels and activating silent information regulator 2 homolog 1 (SIRT1) in cardiomyocytes. METHODS: levels were detected using an NAD test kit. Mitophagy and ferroptosis levels were evaluated by Western blotting, qPCR, JC-1 staining and lipid peroxidation analysis. RESULTS: levels and SIRT1 protein expression were observed in heart of mice and AngII-treated cardiomyocytes. After AKG treatment, these changes were reversed, and increased mitophagy, inhibited ferroptosis, and alleviated damage in cardiomyocytes were observed. When the expression of SIRT1 was inhibited by a selective inhibitor and siRNA, the protective effect of AKG was suppressed. CONCLUSION: , the SIRT-PINK1 and SIRT1-GPX4 signaling pathways are activated to promote mitophagy and inhibit ferroptosis in cardiomyocytes, which ultimately alleviates cardiomyocyte damage.
Yu et al. (Mon,) studied this question.
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