Nonhematopoietic erythropoietin derivative protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis*

ObjectiveCarbamylated EPO(CEPO) is a derivative of erythropoietin(EPO) by subjecting it to carbamylation. It does not stimulate erythropoiesis, but effectively protects tissue from injury. The present study was to investigate the effect of CEPO treatment using in vitro models of hypoxia/reoxygenation(H/R).MethodsCardiomyocytes were exposed to hypoxia(95% N2 and 5% C02) for 1 hour followed by 4 hours of reoxygenation(95% 02 and 5% C02). CEPO was administered after hypoxia, just before reoxygenation. The apoptotic cardiomyocytes were determined by flow cytometry. The level of protein was assessed by western blot analysis.ResultsCEPO treatment significantly decreased the apoptotic cardiomyocytes by 54.20% compared with H/R group. Western blot analysis showed that CEPO administration increased the level of Bcl-2(an antiapoptotic protein) by 62.22% compared with H/R group.ConclusionAcute administration of CEPO protected cardiomyocytes from H/R-induced apoptosis. CEPO protected cardiomyocytes with a concomitant upregulation of Bcl-2 after H/R injury.