Lecithinized copper, zinc-superoxide dismutase ameliorates prolonged hypoxia-induced injury of cardiomyocytes

Recent studies have suggested that prolonged hypoxia results in increased p roduction of reactive oxygen species in cardiomyocytes, which leads to apop tosis of these cells. We previously showed that lecithinized recombinant hu man copper, zinc-superoxide dismutase (rhSOD) showed increased bioavailabil ity through greater membrane affinity and a longer half-life than unmodifie d SOD. The purpose of this study was to investigate whether lecithinized SO D plays a protective role against hypoxic injury in cardiomyocytes. Culture d rat cardiomyocytes incubated with lecithinized SOD (100 U/ml), unmodified SOD (100 U/ml), or vehicle alone were subjected to hypoxia for up to 72 h. Lecithinized SOD, but not unmodified SOD, was successfully delivered intra cellularly, which was verified by Western blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized SOD significantly suppress ed hypoxia-induced cell damage. Since lecithinized SOD also suppressed hypo xia-induced DNA fragmentation, the improved cell survival provided by lecit hinized SOD is thought to be mediated by its antiapoptotic effect. In summa ry, lecithinization resulted in a facilitated rhSOD delivery into cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to prolon ged hypoxia. (C) 2000 Elsevier Science Inc.