The mechanism of nitric oxide and/or superoxide cytotoxicity in endothelial cells.
We examined the mechanism of nitric oxide (NO) and/or superoxide (O2-)-induced cytotoxicity and the importance of thiols in endothelial cells by treating the cells with superoxide dismutase (SOD), catalase (CAT) and hemoglobin (Hb). Pyrogallol, a O2 generator and precursor of hydrogen peroxide (H2O2), had potent cytotoxic effects on the endothelial cells, but this effect was completely abolished by SOD/CAT. Hb, a NO scavenger, protected the endothelial cells from sodium nitroprusside-induced cytotoxicity. The cytotoxic effect of 3-morpholinosydnonimine (SIN-1), which is thought to form peroxynitrite (ONOO-) as a simultaneous O2- and NO generator, was completely blocked by SOD/CAT or Hb. On the other hand, pretreatment of endothelial cells with diethylmaleate, a glutathione depleter, aggravated the cytotoxicity induced by SIN-1, which was prevented by addition of exogenous glutathione and/or SOD/CAT. These data suggest that the cytotoxicity induced by NO, O2- and ONOO- can be blocked by glutathione, and that this is an important cellular protective mechanism against these reactive oxygen species.
College of Pharmacy, Pusan National University, Korea.
H Y
HY
Chung
T
T
Yokozawa
M S
MS
Kim
K H
KH
Lee
K W
KW
Kim
R
R
Yang
J H
JH
Choi
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005978:Glutathione / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000633:toxicity*; D009573:Nitrites / Q000378:metabolism; D011748:Pyrogallol / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism / Q000633:toxicity*
D006454:Hemoglobins; D008298:Maleates; D009566:Nitrates; D009573:Nitrites; D013438:Sulfhydryl Compounds; D011748:Pyrogallol; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D006861:Hydrogen Peroxide; D008981:Molsidomine; D002374:Catalase; D013482:Superoxide Dismutase; C014476:diethyl maleate; D005978:Glutathione