Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in doxorubicin-induced apoptosis in rat cardiac myocytes

Oxidative stress is implicated in the pathogenesis of doxorubicin-induced apoptosis in cardiac myocytes. However, the precise mechanism remains uncertain. We identified an apoptosis-inducing humoral factor, in a conditioned medium from cardiac myocytes subjected to hypoxia/reoxygenation, to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A). We named this novel secreted form of eIF5A, Oxidative stress-Responsive Apoptosis Inducing Protein (ORAIP). We confirmed that ischemia/reperfusion, ultraviolet-irradiation, and ionizing radiation significantly increased plasma levels of ORAIP in vivo, supporting that secretion of ORAIP is specific to the oxidative stress. To investigate the role of ORAIP in doxorubicin-induced apoptosis of cardiac myocytes. Methods: We analyzed plasma levels of ORAIP in rats treated with doxorubicin (10 mg/Kg) in vivo, and the effects of neutralizing anti-ORAIP monoclonal antibody (mAb) on doxorubicin-induced apoptosis of cardiac myocytes in vitro. Results: The (mean ± SE) plasma ORAIP levels before doxorubicin administration were (13.7 ± 2.7) ng/mL, they markedly increased with peak levels ([178.6 ± 6.5] ng/mL, p