Nogo-A Knockdown Inhibits Hypoxia/Reoxygenation-Induced Activation of Mitochondrial-Dependent Apoptosis in Cardiomyocytes

Abstract

Nogo-A has been well-characterized as a potent inhibitor of axonal regeneration and plasticity in the central nervous system, however the role of Nogo-A in non-nervous tissues is essentially unknown. In this study, Nogo-A expression was shown to be significantly increased in left ventricular tissue from human patients with DCM and from patients who have experienced an ischemic event. Nogo-A expression was clearly associated with cardiomyocytes in culture and was localized predominantly in the endoplasmic reticulum. In agreement with the findings from human tissue, Nogo-A expression was significantly increased in cultured cardiomyocytes subjected to hypoxia/reoxygenation. Knockdown of Nogo-A in cardiomyocytes markedly attenuated hypoxia/reoxygenation-induced apoptosis, as indicated by the significant reduction of DNA fragmentation, phosphatidylserine translocation, and caspase-3 cleavage, by a mechanism involving the preservation of mitochondrial membrane potential, the inhibition of ROS accumulation, and the inhibition of cytochrome c release. Together, these data indicate that knockdown of Nogo-A in cardiomyocytes may serve as a novel therapeutic strategy in the treatment of ischemic/hypoxic injury. Correction et al.Biophysical JournalMay 04, 2011In Brief212-Pos. Full-Text PDF Open Archive