title: Disruption of protein tyrosine phosphate homeostasis in bronchial epithelial cells exposed to oil fly ash.
abstract: Residual oil fly ash (ROFA) is a toxic air pollutant that we have previously shown induces inflammatory mediator expression in human bronchial epithelial cells. To identify intracellular signaling mechanisms activated by ROFA, we studied its effect on protein tyrosine phosphate metabolism in the human bronchial epithelial cell line BEAS. Noncytotoxic levels of ROFA induced significant dose- and time-dependent increases in protein tyrosine phosphate levels in BEAS cells. ROFA-induced increases in protein phosphotyrosines were associated with its soluble fraction and were mimicked by vanadyl [V(IV)]- and vanadate [V(V)]-containing solutions. Ferrous, ferric, and nickel (II) ion solutions failed to increase phosphotyrosine levels. Tyrosine phosphatase activity, which was known to be inhibited by vanadium ions, was markedly diminished after ROFA treatment. Tyrosine kinase activity was unaffected. We conclude that ROFA exposure induces vanadium ion-mediated inhibition of tyrosine phosphatase activity, leading to accumulation of protein phosphotyrosines in BEAS cells. These findings demonstrate that ROFA exposure disrupts protein tyrosine phosphate homeostasis in BEAS cells and suggest a possible mechanism that leads to increased synthesis of proinflammatory proteins in airway epithelial cells exposed to PM10.
authors.affiliation: Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, 27599-7310, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Samet
authors.forename: J
authors.initials: J
authors.lastname: Stonehuerner
authors.forename: W
authors.initials: W
authors.lastname: Reed
authors.forename: R B
authors.initials: RB
authors.lastname: Devlin
authors.forename: L A
authors.initials: LA
authors.lastname: Dailey
authors.forename: T P
authors.initials: TP
authors.lastname: Kennedy
authors.forename: P A
authors.initials: PA
authors.lastname: Bromberg
authors.forename: A J
authors.initials: AJ
authors.lastname: Ghio
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002244:Carbon / Q000633:toxicity; D002478:Cells, Cultured; D060729:Coal Ash; D004848:Epithelium / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007220:Industrial Waste; D008970:Molecular Weight; D009821:Oils; D052638:Particulate Matter; D010750:Phosphoproteins / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D060729:Coal Ash; D007220:Industrial Waste; D009821:Oils; D052638:Particulate Matter; D010750:Phosphoproteins; D019000:Phosphotyrosine; D002244:Carbon; D011505:Protein-Tyrosine Kinases; D017027:Protein Tyrosine Phosphatases