Reactive oxygen and nitrogen metabolites modulate fibronectin-induced fibroblast migration in vitro

Nitration of proteins by peroxynitrite may alter protein function. We hypot hesized that reactive nitrogen species modulate fibronectin-induced fibrobl ast migration. To test this hypothesis, we evaluated fibroblast migration i nduced by fibronectin incubated with and without peroxynitrite. Peroxynitri te attenuated fibronectin-induced fibroblast migration in a dose-dependent manner but did not attenuate complement-activated serum-induced fibroblast migration. The reducing agents, deferoxamine and dithiothreitol (DTT), and L-tyrosine reversed the inhibition by peroxynitrite. PAPA-NONOate, a nitric oxide (NO) donor, and superoxide generated by the action of xanthine oxida se on lumazine or xanthine, also showed an inhibitory effect on fibroblast migration. The peroxynitrite generator, 3-morpholinosydnonimine (SIN-1), ca used a concentration-dependent inhibition of fibroblast migration. Peroxyni trite reduced fibronectin binding to fibroblasts and resulted in nitrotyros ine formation. These findings are consistent with nitration of tyrosine by peroxynitrite with subsequent inhibition of fibronectin binding to fibrobla sts and suggest that peroxynitrite may play a role in regulation of fibrobl ast migration. (C) 2000 Elsevier Science Inc.