title: Inhibition of NADH/NADPH oxidase affects signal transduction by growth factor receptors in normal fibroblasts.
abstract: 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.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, Naples 80131, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Ammendola
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ruocchio
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Chirico
authors.forename: Lucia
authors.initials: L
authors.lastname: Russo
authors.forename: Carmela
authors.initials: C
authors.lastname: De Felice
authors.forename: Franca
authors.initials: F
authors.lastname: Esposito
authors.forename: Tommaso
authors.initials: T
authors.lastname: Russo
authors.forename: Filiberto
authors.initials: F
authors.lastname: Cimino
mesh_terms: 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
chemical_list: 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