Lecithinized copper, zinc-superoxide dismutase ameliorates prolonged hypoxia-induced injury of cardiomyocytes.
Recent studies have suggested that prolonged hypoxia results in increased production of reactive oxygen species in cardiomyocytes, which leads to apoptosis of these cells. We previously showed that lecithinized recombinant human copper, zinc-superoxide dismutase (rhSOD) showed increased bioavailability through greater membrane affinity and a longer half-life than unmodified SOD. The purpose of this study was to investigate whether lecithinized SOD plays a protective role against hypoxic injury in cardiomyocytes. Cultured 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 intracellularly, which was verified by Western blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized SOD significantly suppressed hypoxia-induced cell damage. Since lecithinized SOD also suppressed hypoxia-induced DNA fragmentation, the improved cell survival provided by lecithinized SOD is thought to be mediated by its antiapoptotic effect. In summary, lecithinization resulted in a facilitated rhSOD delivery into cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to prolonged hypoxia.
Nakajima
H
H
Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
Ishizaka
N
N
Hangaishi
M
M
Taguchi
J
J
Itoh
J
J
Igarashi
R
R
Mizushima
Y
Y
Nagai
R
R
Ohno
M
M
D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004249:DNA Damage; D004337:Drug Carriers; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D009206:Myocardium / Q000473:pathology*; D010713:Phosphatidylcholines; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology
D004337:Drug Carriers; D010713:Phosphatidylcholines; D011994:Recombinant Proteins; D013482:Superoxide Dismutase