title: OH-Radical Specific Addition to Glutathione S-Atom at the Air-Water Interface: Relevance to the Redox Balance of the Lung Epithelial Lining Fluid.
abstract: Antioxidants in epithelial lining fluids (ELF) prevent inhaled air pollutants from reaching lung tissue. This process, however, may upset ELF's redox balance, which is deemed to be expressed by the ratio of the major antioxidant glutathione (GSH) to its putative oxidation product GSSG. Previously, we found that at physiological pH O3(g) rapidly oxidizes GS(2-)(aq) (but not GSH(-)) to GSO3(-) rather than GSSG. Here, we report that in moderately acidic pH ≤ 5 media ·OH(g) oxidizes GSH(-)(aq) to sulfenic GSOH(-), sulfinic GSO2(-), and sulfonic GSO3(-) acids via ·OH specific additions to reduced S-atoms. The remarkable specificity of ·OH on water versus its lack of selectivity in bulk water implicates an unprecedented steering process during [OH···GSH] interfacial encounters. Thus, both O3 and ·OH oxidize GSH to GSOH(-) under most conditions, and since GSOH(-) is reduced back to GSH in vivo by NADPH, redox balance may be in fact signaled by GSH/GSOH ratios.
authors.affiliation: The Hakubi Center for Advanced Research, Kyoto University , Kyoto 606-8302, Japan.|Research Institute for Sustainable Humanosphere, Kyoto University , Uji 611-0011, Japan.|PRESTO, Japan Science and Technology Agency , Kawaguchi 332-0012, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Enami
authors.affiliation: Linde Center for Global Environmental Science, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hoffmann
authors.affiliation: Linde Center for Global Environmental Science, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Agustín J
authors.initials: AJ
authors.lastname: Colussi
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D004848:Epithelium / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry*; D008168:Lung / Q000378:metabolism*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction
chemical_list: D017665:Hydroxyl Radical; D005978:Glutathione
keywords: Fenton; PM2.5; reactive oxygen species; toxicology; uptake