Inhibition of NADH/NADPH Oxidase Affects Signal Transduction by Growth Factor Receptors in Normal Fibroblasts

Author: Ammendola R.   Ruocchio M.R.   Chirico G.   Russo L.   de Felice C.   Esposito F.   Russo T.   Cimino F.  

Publisher: Elsevier

ISSN: 0003-9861

Source: Archives of Biochemistry and Biophysics, Vol.397, Iss.2, 2002-01, pp. : 253-257

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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 p21waf1 accumulation that occurs when cells are exposed to growth factors. Finally, NADH/NADPH inhibitors prevent the p66Shc 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. ©2002 Elsevier Science.

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