title: Sustained nitric oxide delivery delays nitric oxide-dependent apoptosis in macrophages: contribution to the physiological function of activated macrophages.
abstract: Treatment of the macrophage cell line RAW 264.7 with the short-lived NO donor S-nitrosoglutathione triggers apoptosis through the release of mitochondrial mediators. However, continuous supply of NO by long-lived NO donors protected cells from apoptosis through mechanisms that involved the maintenance or an increase in the levels of the inhibitor of apoptosis proteins (IAPs) cIAP-1, cIAP-2, and xIAP and decreases in the accumulation of p53 and in the levels and targeting of Bax to the mitochondria. As a result of these changes, the activation of caspases 9 and 3 was notably delayed, expanding the time of viability of the macrophages. Moreover, inhibition of NO synthase 2 activity after 8 h of stimulation of RAW 264.7 cells with LPS and IFN-gamma accelerated apoptosis via an increase in the processing and activation of caspases. These data suggest that NO exerts an important role in the autoregulation of apoptosis in macrophages.
authors.affiliation: Instituto de Bioquímica (Centro Mixto Consejo Superior de Investigaciones Científicas-Universidad Complutense) and Centro Nacional de Investigaciones Cardiovasculares, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
authors.forename: Sonsoles
authors.initials: S
authors.lastname: Hortelano
authors.forename: Paqui G
authors.initials: PG
authors.lastname: Través
authors.forename: Miriam
authors.initials: M
authors.lastname: Zeini
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Alvarez
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D013997:Time Factors; D014226:Triazenes / Q000494:pharmacology
chemical_list: C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D014226:Triazenes; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D007371:Interferon-gamma; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases