title: Prevention of free-radical induced apoptosis by induction of human recombinant Cu, Zn-SOD in pig endothelial cells.
abstract: Vascular endothelial cells are the prime target in ischemia reperfusion injury. Growing evidence has shown that one of the main etiologies is considered to be reactive oxygen species (ROS) that induce endothelial-cell death either by necrosis or apoptosis. Cultured porcine endothelial cells were transfected with human copper, zinc-superoxide dismutase (h-Cu, Zn-SOD) to investigate whether these cells can prevent apoptosis from oxidative injury in vitro. The endothelial cells were cultured with SIN-1 (3-morpholinosydnonimine-N-ethylcarbanride) as a donor of peroxinitrite (ONOO(-)). The control cells without the gene transfection developed characteristic apoptotic changes both morphologically and biochemically when they were incubated with SIN-1 of 200 M. However, the cells showed necrosis predominantly when the concentration of SIN-1 was 1,000 M. On the other hand, the cells transfected with h-Cu, Zn-SOD showed significantly less evidence of apoptotic change after exposure to SIN-1. Nitric oxide (NO) did not significantly affect the viability of either the control cells or the transfected cells. One of the potent ROS, peroxinitrite, is considered to play a significant role in ischemia reperfusion injury. SIN-1 can produce peroxinitrite in vitro that induces endothelial-cell damage by apoptosis. This type of cytotoxicity can be successfully prevented by transfection of the h-Cu, Zn-SOD into the cells.
authors.affiliation: Nagoya University, School of Medicine, Department of Surgery II, 65 Tsurumai-cho, Showa-ku, Japan. itsuyoko@med.nagoya-u.ac.jp
authors.forename: Itsuo
authors.initials: I
authors.lastname: Yokoyama
authors.forename: Masataka
authors.initials: M
authors.lastname: Negita
authors.forename: Da-Ge
authors.initials: DG
authors.lastname: Liu
authors.forename: Takaharu
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Akemi
authors.initials: A
authors.lastname: Hayakawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Hayashi
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D013552:Swine; D014183:Transplantation, Heterologous / Q000502:physiology
chemical_list: D005609:Free Radicals; D020030:Nitric Oxide Donors; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; C002385:linsidomine; D008981:Molsidomine; D013482:Superoxide Dismutase