Inhibition of GSDMD Activates Poly(ADP-ribosyl)ation and Promotes Myocardial Ischemia-Reperfusion Injury.

ABSTRACT: The precise control of cardiomyocyte viability is imperative to combat myocardial ischemia-reperfusion injury (I/R), in which apoptosis and pyroptosis putatively contribute to the process. Recent researches indicated that GSDMD is involved in I/R as an executive protein of pyroptosis. However, its effect on other forms of cell death is unclear. We identified that GSDMD and GSDMD-N levels were significantly upregulated in the I/R myocardium of mice. Knockout of GSDMD conferred the resistance of the hearts to reperfusion injury in the acute phase of I/R but aggravated reperfusion injury in the chronic phase of I/R. Mechanistically, GSDMD deficiency induced the activation of PARylation and the consumption of NAD⁺ and ATP, leading to cardiomyocyte apoptosis. Moreover, PJ34, a putati

SUBMITTER: Zhang ZH 

PROVIDER: S-EPMC9249530 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature