The survival of skeletal muscle myoblasts in vitro is sensitive to a donor of nitric oxide and superoxide, SIN-1, but not to nitric oxide or peroxynitrite alone.
The survival of skeletal muscle myoblasts in culture after exposure either to a donor of NO, sodium nitroprusside (SNP), or ethanamine, 2,2'-(hydroxynitrosohydrazono)bis-(DETA NONOate), or to a donor of both NO and O(-)(2), 3-morpholinosydnonimine hydrochloride (SIN-1), was investigated. SIN-1 reduced clonogenic survival markedly but donors of NO alone did not. The injurious effect of SIN-1 was prevented by oxyhemoglobin or by uric acid but not by superoxide dismutase. The exposure of myoblasts to authentic peroxynitrite (ONOO(-)) or to DETA NONOate in the presence of an O(-)(2)-generating system did not reduce their survival. The results show that NO or ONOO(-) alone is not detrimental to myoblast survival and suggest that SIN-1 toxicity is, at least in part, mediated by H(2)O(2) in this myoblast culture system.
Lepore
D A
DA
Bernard O'Brien Institute of Microsurgery, St. Vincent's Hospital, Fitzroy, Melbourne, 3065, Australia. d.lepore@surgery.svh.unimelb.edu.au
Stewart
A G
AG
Tomasi
A
A
Anderson
R L
RL
Hurley
J V
JV
Morrison
W A
WA
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects*; D009566:Nitrates / Q000494:pharmacology / Q000633:toxicity*; D009569:Nitric Oxide / Q000494:pharmacology / Q000633:toxicity*; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000633:toxicity*; D009603:Nitroso Compounds / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology / Q000633:toxicity*; D014527:Uric Acid / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D009566:Nitrates; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D013481:Superoxides; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; C039642:peroxynitric acid; D014527:Uric Acid; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase