title: Specific protein nitration in nitric oxide-induced apoptosis of human monocytes.
abstract: The sustained overproduction of nitric oxide (NO) observed in inflammatory conditions can contribute to cell demise by affecting apoptosis. Nitration of tyrosine residues occurs in a range of diseases involving macrophage activation. Since NO induces apoptosis in monocytes/macrophages, we tested the hypothesis that nitration of specific proteins could result in apoptotic cell death. The peroxynitrite generator SIN-1 promoted apoptosis in monocytes based on oligonucleosomal DNA fragmentation, caspase-3 and -9 activation, Bcl-2 depletion and accumulation of Bax and p53 proteins. We also found that the signaling pathway triggered by SIN-1 was initiated through tyrosine kinase and Rac activation and resulted in increased JNK and p38 activities. Among the tyrosine-nitrated proteins, Rac and Lyn were identified. Using specific inhibitors for different signaling and effector molecules involved in the apoptotic process we demonstrate that NO, via protein-nitration, could play an important role in controlling the inflammatory response by regulation of monocyte homeostasis.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad de Navarra, C/ Irunlarrea 1, 31008 Pamplona, Navarra, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Natal
authors.forename: Teresa
authors.initials: T
authors.lastname: Modol
authors.forename: Juan A
authors.initials: JA
authors.lastname: Osés-Prieto
authors.forename: Natalia
authors.initials: N
authors.lastname: López-Moratalla
authors.forename: María J
authors.initials: MJ
authors.lastname: Iraburu
authors.forename: María J
authors.initials: MJ
authors.lastname: López-Zabalza
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D053938:DNA Fragmentation; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009584:Nitrogen / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D009569:Nitric Oxide; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D053453:Caspase 9; D009584:Nitrogen