title: Peroxynitrite induces GADD34, 45, and 153 VIA p38 MAPK in human neuroblastoma SH-SY5Y cells.
abstract: Peroxynitrite, one of the most reactive radicals, is produced from superoxide anion and nitric oxide. A peroxynitrite generator, 3-morpholinosydonimine (SIN-1), was found to induce the expression of three different growth arrest and DNA damage-inducible (GADD) mRNA, GADD34, GADD45, and GADD153, at the early phase during cell death in human neuroblastoma SH-SY5Y cells. In addition, peroxynitrite activated p38 MAPK just before induction of three GADD mRNA. A specific inhibitor of p38 MAPK, SB202190, markedly suppressed peroxynitrite-induced expression of three GADD mRNA in SH-SY5Y cells. The expression of three GADD genes and also p38 MAPK phosphorylation were suppressed by treatment with radical scavengers, superoxide dismutase plus catalase and glutathione. Glutathione depletion by L-buthionine-S, R-sulfoximine (BSO), increased the vulnerability of the cells to peroxynitrite. These findings indicate that peroxynitrite-mediated oxidative stress activated p38 MAPK to induce three GADD genes.
authors.affiliation: Laboratory of Biochemistry and Metabolism, Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Oh-Hashi
authors.forename: W
authors.initials: W
authors.lastname: Maruyama
authors.forename: K
authors.initials: K
authors.lastname: Isobe
mesh_terms: D000943:Antigens, Differentiation; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D004249:DNA Damage / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics*; D009566:Nitrates / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000943:Antigens, Differentiation; D000975:Antioxidants; D022762:CCAAT-Enhancer-Binding Proteins; D018797:Cell Cycle Proteins; D005978:Glutathione; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases; D008981:Molsidomine; D009363:Neoplasm Proteins; D009566:Nitrates; D054645:Protein Phosphatase 1; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011725:Pyridines; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D000097642:GADD45 Proteins; D000099190:MAP-Kinase-Activated Kinase 2; C497249:DDIT3 protein, human; C039642:peroxynitric acid; C002385:linsidomine; C087519:PPP1R15A protein, human; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole