Upregulation of iASPP ameliorates hypoxia/reoxygenation-induced apoptosis and oxidative stress in cardiomyocytes by upregulating Nrf2 signaling.

Abstract

The inhibitor of apoptosis-stimulating protein of p53 (iASPP) acts as a key modulator of cellular protection against oxidative stress. In the present work, we assessed the role of iASPP in the regulation of cardiomyocyte injury induced by hypoxia/reoxygenation (H/R). We found that H/R-exposed cardiomyocytes expressed decreased levels of iASPP. The upregulation of iASPP repressed H/R-induced injury by decreasing levels of apoptosis and reactive oxygen species production. The upregulation of iASPP increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation and enhanced Nrf2 activation. The overexpression of Kelch-like ECH-associated protein 1 reversed iASPP-mediated promotion of Nrf2 activation. Nrf2 inhibition abrogated iASPP-mediated cardioprotective effects in H/R-exposed cardiomyocytes. Our work demonstrates that the upregulation of iASPP ameliorates H/R-induced apoptosis and oxidative stress in cardiomyocytes via potentiating Nrf2 signaling via modulation of Keap1.