Abstract 15032: Oxygen Induces a p53-Dependent NOS3-Mediated Survival Pathway in the Infarct Myocardium by Regulating p53(Lys120) Acetylation and p53 DNA Interaction

We have recently showed that supplemental oxygen (Ox), administered as 100% O2, 60 min/day for 2 wk, was capable of promoting NOS3-dependent myocyte survival in the infarct (MI) heart. Interestingly, the proapoptotic p53, which is known to transcriptionally regulate members of the NOS family, was consistently overexpressed in the MI+Ox hearts (Fig A) with higher survival potential when compared to MI hearts. We hypothesized that p53 plays an oxygen-dependent dual role in generating apoptotic signals in the MI hearts and NOS3-mediated survival signals in the MI+Ox hearts. A 23-bp p53 response element (p53RE) was identified in NOS3 promoter and p53 was found to directly bind and transcriptionally regulate NOS3 promoter in the MI+Ox hearts. p53 from the MI heart did not bind to NOS3-p53RE and showed affinity towards apoptotic BAX-p53RE. p53 from MI+Ox heart showed affinity towards NOS3-p53RE. Analysis of p53 post-translational modifications showed differential acetylation of p53 core-domain at p53(Lys120) re...