title: Role of H2O2 in the oxidative effects of zinc exposure in human airway epithelial cells.
abstract: Human exposure to particulate matter (PM) is a global environmental health concern. Zinc (Zn(2+)) is a ubiquitous respiratory toxicant that has been associated with PM health effects. However, the molecular mechanism of Zn(2+) toxicity is not fully understood. H2O2 and Zn(2+) have been shown to mediate signaling leading to adverse cellular responses in the lung and we have previously demonstrated Zn(2+) to cause cellular H2O2 production. To determine the role of Zn(2+)-induced H2O2 production in the human airway epithelial cell response to Zn(2+) exposure. BEAS-2B cells expressing the redox-sensitive fluorogenic sensors HyPer (H2O2) or roGFP2 (EGSH) in the cytosol or mitochondria were exposed to 50µM Zn(2+) for 5min in the presence of 1µM of the zinc ionophore pyrithione. Intracellular H2O2 levels were modulated using catalase expression either targeted to the cytosol or ectopically to the mitochondria. HO-1 mRNA expression was measured as a downstream marker of response to oxidative stress induced by Zn(2+) exposure. Both cytosolic catalase overexpression and ectopic catalase expression in mitochondria were effective in ablating Zn(2+)-induced elevations in H2O2. Compartment-directed catalase expression blunted Zn(2+)-induced elevations in cytosolic EGSH and the increased expression of HO-1 mRNA levels. Zn(2+) leads to multiple oxidative effects that are exerted through H2O2-dependent and independent mechanisms.
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Wages
authors.affiliation: EPHD, NHEERL, US Environmental Protection Agency, Chapel Hill, NC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Silbajoris
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Speen
authors.affiliation: CEMALB, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Brighton
authors.affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Henriquez
authors.affiliation: EPHD, NHEERL, US Environmental Protection Agency, Chapel Hill, NC, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Tong
authors.affiliation: CEMALB, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Bromberg
authors.affiliation: ISTD, NHEERL, US Environmental Protection Agency, RTP, NC, USA.
authors.forename: Steven O
authors.initials: SO
authors.lastname: Simmons
authors.affiliation: EPHD, NHEERL, US Environmental Protection Agency, Chapel Hill, NC, USA. Electronic address: Samet.James@epa.gov.
authors.forename: James M
authors.initials: JM
authors.lastname: Samet
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D006861:Hydrogen Peroxide; D002374:Catalase; D051547:Heme Oxygenase-1; D005978:Glutathione; D015032:Zinc
keywords: Catalase; Genetically encoded redox probes; H(2)O(2); Live cell imaging; Mitochondria; Zinc