title: Variable overoxidation of peroxiredoxins in human lung cells in severe oxidative stress.
abstract: Peroxiredoxins (Prxs) are a group of thiol containing proteins that participate both in signal transduction and in the breakdown of hydrogen peroxide (H(2)O(2)) during oxidative stress. Six distinct Prxs have been characterized in human cells (Prxs I-VI). Prxs I-IV form dimers held together by disulfide bonds, Prx V forms intramolecular bond, but the mechanism of Prx VI, so-called 1-Cys Prx, is still unclear. Here we describe the regulation of all six Prxs in cultured human lung A549 and BEAS-2B cells. The cells were exposed to variable concentrations of H(2)O(2), menadione, tumor necrosis factor-alpha or transforming growth factor-beta. To evoke glutathione depletion, the cells were furthermore treated with buthionine sulfoximine. Only high concentrations (300 microM) of H(2)O(2) caused a minor increase (<28%, 4 h) in the expression of Prxs I, IV, and VI. Severe oxidant stress (250-500 microM H(2)O(2)) caused a significant increase in the proportion of the monomeric forms of Prxs I-IV; this was reversible at lower H(2)O(2) concentrations (< or =250 microM). This recovery of Prx overoxidation differed among the various Prxs; Prx I was recovered within 24 h, but recovery required 48 h for Prx III. Overall, Prxs are not significantly modulated by mild oxidant stress or cytokines, but there is variable, though reversible, overoxidation in these proteins during severe oxidant exposure.
authors.affiliation: Department of Internal Medicine, University of Oulu, Oulu University Hospital, Finland.
authors.forename: Siri T
authors.initials: ST
authors.lastname: Lehtonen
authors.forename: Piia M H
authors.initials: PM
authors.lastname: Markkanen
authors.forename: Mirva
authors.initials: M
authors.lastname: Peltoniemi
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010544:Peroxidases / Q000378:metabolism*; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D016877:Oxidants; D006861:Hydrogen Peroxide; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins