title: Mitochondrial-mediated apoptosis pathway in alveolar epithelial cells exposed to the metals in combustion-generated particulate matter.
abstract: Previously a significant mitochondrial impairment was identified in alveolar epithelial cells exposed to metals adsorbed to combustion-generated particulate matter (PM). Due to the critical role of mitochondria in apoptosis, the aim of this study was to investigate the pro-apoptotic potential of metals present in oil fly ash (OFA). A549 cells were exposed to water-soluble components of an OFA sample, containing vanadium [V(IV)], iron [Fe(III)], and nickel [Ni(II)] (68.8, 110.4, and 18 μM, respectively). Experiments were also performed using individual metal solutions. Apoptosis was detected and the mitochondrial role was assessed by a caspase-9 inhibitor (Z-LEHD-FMK). To determine whether the presence of impaired mitochondria in unexposed daughter cells increased apoptosis, an in vitro model was developed that allowed determination of effects until the third cell generation. To specifically examine the toxicity of vanadium (V), that characterize the airborne pollutant examined in this study, p53involvement and metabolic impairment through changes in HIF-1α and Glut-1 expression were determined. OFA and individual metal solutions produced significant apoptosis in the progeny of exposed cells, triggering the intrinsic apoptosis pathway. In apoptosis induced by poorly genotoxic metal V, p53 did not play a significant role. However, V exposure increased nuclear translocation of HIF-1α and expression of the Glut-1 receptor, indicating metabolic impairment due to metal-induced mitochondrial dysfunction. Overall, these results improve our knowledge of the pathogenic role that airborne metals and in particular V exerted in respiratory epithelium.
authors.affiliation: a Department of Biomedical Sciences and Morphological and Functional Images , University of Messina , Messina , Italy.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.forename: Barbara
authors.initials: B
authors.lastname: Baluce
authors.forename: Maria
authors.initials: M
authors.lastname: Bertuccio
authors.forename: Isa
authors.initials: I
authors.lastname: Picerno
authors.forename: Angela
authors.initials: A
authors.lastname: Di Pietro
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D060729:Coal Ash / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects; D009532:Nickel / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects; D014639:Vanadium / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D060729:Coal Ash; D014639:Vanadium; D009532:Nickel; D007501:Iron