GDF11 replenishment protects against hypoxia-mediated apoptosis in cardiomyocytes by regulating autophagy.

GDF11 replenishment protects against hypoxia-mediated apoptosis in cardiomyocytes by regulating autophagy.
Eur J Pharmacol. 2020 Aug 27;:173495
Authors: Jiao L, Shao Y, Yu Q, Li M, Wang Y, Gong M, Yang X, Liu T, Li Z, Liu H, Zhang Y, Tan Z, Sun L, Xuan L, Yin H, Zhang Y, Cai B, Zhang Y, Yang B
Abstract
GDF11 has been reported to play a critical role in rejuvenating hypertrophy heart, skeletal muscle, and blood vessel regeneration in aged mice. Whether GDF11 can regulate autophagy in cardiomyocytes remains largely unknown. Thus, the purpose of the present study was to investigate the effects of GDF11 on cardiomyocyte autophagy induced by hypoxia, in addition to the underlying mechanisms. By using the MTT assay, Flow cytometry assay, LIVE/DEAD® Viability/Cytotoxicity Kit Stains and TUNEL assay, we found that exogenous GDF11 decreased apoptosis caused by prolonged hypoxia in cardiomyocytes. The expression of GDF11 was decreased obviously both in the cardiac tissue of myocardial infarction mice and the hypoxia treated cardiomyocytes. Protein levels of cleaved caspase-3, p-AMPK, SQSTM1, LC3B-I/II and GDF11 were detected by western blot. Autophagosomes and autolysosomes were identified by confocal laser microscopy after transfecting with the mREP-eGFP-LC3 plasmids. Antibody against GDF11 (anti-GDF11) was used to inhibit the function of GDF11. At the molecular level, exogenous GDF11 increased AMPK function and enhanced autophagy activity. ...

Source: European Journal of Pharmacology - August 26, 2020 Category: Drugs & Pharmacology Authors: Jiao L, Shao Y, Yu Q, Li M, Wang Y, Gong M, Yang X, Liu T, Li Z, Liu H, Zhang Y, Tan Z, Sun L, Xuan L, Yin H, Zhang Y, Cai B, Zhang Y, Yang B Tags: Eur J Pharmacol Source Type: research