Specific protein nitration in nitric oxide-induced apoptosis of human monocytes |
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Authors: | Cristina Natal Teresa Modol Juan A. Osés-Prieto Natalia López-Moratalla María J. Iraburu María J. López-Zabalza |
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Affiliation: | (1) Departamento de Bioquímica y Biología Molecular, Universidad de Navarra, C/ Irunlarrea 1, 31008 Pamplona, Navarra, Spain |
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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. |
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Keywords: | Human monocytes Nitric oxide Protein nitration Signaling pathways Apoptosis |
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