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 H2O2 in this myoblast culture system.