Peroxynitrite induces GADD34, 45, and 153 via p38 MAPK in human neuroblastoma, SH-SY5Y cells

Peroxynitrite, one of the most reactive radicals, is produced from superoxi de anion and nitric oxide. A peroxynitrite generator, 3-morpholinosydonimin e (SIN-1), was found to induce the expression of three different growth arr est and DNA damage-inducible (GADD) mRNA, GADD34, GADD45, and CADD153, at t he early phase during cell death in human neuroblastoma SH-SYSY cells. In a ddition, peroxynitrite activated p38 MAPK just before induction of three GA DD mRNA. A specific inhibitor of p38 MAPK, SB202190, markedly suppressed pe roxynitrite-induced expression of three GADD mRNA in SH-SYSY cells. The exp ression of three GADD genes and also p38 MAPK phosphorylation were suppress ed by treatment with radical scavengers, superoxide dismutase plus catalase and glutathione. Glutathione depletion by L-buthionine-S, R-sulfoximine (B SO), increased the vulnerability of the cells to peroxynitrite. These findi ngs indicate that peroxynitrite-mediated oxidative stress activated p38 MAP K to induce three GADD genes. (C) 2001 Elsevier Science Inc.