title: Mitochondrial oxidant production by a pollutant dust and NO-mediated apoptosis in human alveolar macrophage.
abstract: Residual oil fly ash (ROFA) is a pollutant dust that stimulates production of reactive oxygen species (ROS) from mitochondria and apoptosis in alveolar macrophages (AM), but the relationship between these two processes is unclear. In this study, human AM were incubated with ROFA or vanadyl sulfate (VOSO(4)), the major metal constituent in ROFA, with or without nitro-L-arginine methyl ester (L-NAME), diphenyleneiodonium (DPI), and mitochondrial electron transport inhibitors. Interactions among production of ROS, nitric oxide (NO), and apoptosis of AM were determined. ROFA-stimulated ROS production was attenuated by DPI, rotenone, antimycin, and NaN(3), but not by L-NAME, a pattern mimicked by VOSO(4). ROFA-induced apoptosis was inhibited by L-NAME and a caspase-3-like protease inhibitor, but not by mitochondrial inhibitors. ROFA enhanced NO-mediated increase in caspase-3-like activity. VOSO(4) had minor effects on apoptosis. Thus ROFA-stimulated production of ROS from mitochondria was independent of apoptosis of AM, which was mediated by activation of caspase-3-like proteases and NO. The pro-oxidant effect but not the proapoptotic effect of ROFA was mediated by vanadium.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, Environmental Protection Agency, Research Triangle Park, NC 27711, USA. huang.tony@epa.gov
authors.forename: Yuh-Chin T
authors.initials: YC
authors.lastname: Huang
authors.forename: Joleen
authors.initials: J
authors.lastname: Soukup
authors.forename: Shirley
authors.initials: S
authors.lastname: Harder
authors.forename: Susanne
authors.initials: S
authors.lastname: Becker
mesh_terms: D000393:Air Pollutants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002244:Carbon / Q000494:pharmacology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D060729:Coal Ash; D004305:Dose-Response Relationship, Drug; D004391:Dust; D006801:Humans; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D016877:Oxidants / Q000096:biosynthesis*; D052638:Particulate Matter; D017382:Reactive Oxygen Species / Q000378:metabolism; D014639:Vanadium / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D060729:Coal Ash; D004391:Dust; D016877:Oxidants; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D014639:Vanadium; D009569:Nitric Oxide; D002244:Carbon; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D019331:NG-Nitroarginine Methyl Ester