Inhibition of NADH/NADPH oxidase affects signal transduction by growth factor receptors in normal fibroblasts.
Reactive oxygen species have been implicated as possible second messengers in mitogenic signal transduction. We demonstrate that in normal fibroblasts the treatment with the two inhibitors of phagocytic NADH/NADPH oxidase prevents tyrosine phosphorylation of platelet-derived growth factor receptor upon the exposure of serum-deprived cells to growth factors. Furthermore, the inhibition of NADH/NADPH oxidase abolishes ERKs activation and p21(waf1) accumulation that occurs when cells are exposed to growth factors. Finally, NADH/NADPH inhibitors prevent the p66(Shc) Ser-phosphorylation induced by serum and by phorbol 12-myristate-13-acetate, which suggests that the direct target(s) of reactive oxygen species is(are) located upstream from the machinery connecting growth factor receptors to Ras.
Ammendola
Rosario
R
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, Naples 80131, Italy.
Ruocchio
Maria Rosaria
MR
Chirico
Giuseppa
G
Russo
Lucia
L
De Felice
Carmela
C
Esposito
Franca
F
Russo
Tommaso
T
Cimino
Filiberto
F
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001769:Blood; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D051381:Rats; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology
D003470:Culture Media; D004791:Enzyme Inhibitors; D009861:Onium Compounds; D017978:Receptors, Growth Factor; D013450:Sulfones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; C007517:diphenyleneiodonium; D009247:NADH, NADPH Oxidoreductases; D000111:Acetylcysteine