PARP1 promote autophagy in cardiomyocytes via modulating FoxO3a transcription.

Autophagy is a key regulatory process in maintaining cellular homoeostasis via lysosome degradation. Growing evidence reveals that poly(ADP-ribose) polymerase-1 is involved in the progression of many cardiovascular diseases. This study was undertaken to discuss the role of in cardiomyocyte autophagy. Our results demonstrated that Pduanyu371 was activated in response to starvation-induced myocardial autophagy. We identified Forkhead box O (FoxO)3a as a substrate of Upon Pduanyu371 activation, poly(ADP-ribosyl)ation dissociated histone H1 from FoxO3a target gene promoter and promoted FoxO3a nuclear accumulation and binding activity to the target promoters, resulting in increased expression of autophagy related genes. Activated autophagy by Pduanyu371 impaired mitochondrial metabolism and promoted cardiomyocyte death. And Pduanyu371 silencing or specific inhibitors alleviated the promotion of FoxO3 activity upon starvation or myocardial ischemia, thus suppressing cardiac apoptosis and fibrosis. Together, these data indicate that poly(ADP-ribosyl)ation of FoxO3a plays a key role in cardiomyocyte autophagy. The utilization of Pduanyu371 as a therapeutic target for related cardiovascular diseases would be desirable.

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