Gasdermin D mediates endoplasmic reticulum stress via FAM134B to regulate cardiomyocyte autophagy and apoptosis in doxorubicin-induced cardiotoxicity.

ABSTRACT: Cardiomyocyte pyroptosis and apoptosis play a vital role in the pathophysiology of several cardiovascular diseases. Our recent study revealed that gasdermin D (GSDMD) can promote myocardial I/R injury via the caspase-11/GSDMD pathway. We also found that GSDMD deletion attenuated myocardial I/R and MI injury by reducing cardiomyocyte apoptosis and pyroptosis. However, how GSDMD mediates cardiomyocyte apoptosis and protects myocardial function remains unclear. Here, we found that doxorubicin (DOX) treatment resulted in increased apoptosis and pyroptosis in cardiomyocytes and that caspase-11/GSDMD could mediate DOX-induced cardiotoxicity (DIC) injury. Interestingly, GSDMD overexpression promoted cardiomyocyte apoptosis, which was attenuated by GSDMD knockdown. Notably, GSDMD overexpression ex

SUBMITTER: Qu Y 

PROVIDER: S-EPMC9606128 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature