title: In vivo and in vitro evidence for epidermal H2O2-mediated oxidative stress in piebaldism.
abstract: Piebaldism is characterised by the absence of pigment in patches on the skin, usually present at birth. Mutations in the kit gene are documented. Clinically this disorder can mimic vitiligo. Here, we show for the first time the presence of oxidised pteridine-induced fluorescence in association with H2O2-mediated stress in piebald patches employing Wood's light and in vivo FT-Raman spectroscopy. In situ immunofluorescence data revealed low catalase and methionine sulphoxide reductase A (MSRA) levels whereas thioredoxin reductase and methionine sulphoxide reductase B (MSRB) are not affected. We also show low superoxide dismutase levels in these patients. The presence of thioredoxin reductase provides capacity to reduce H2O2, a mechanism which is absent in vitiligo. Importantly, this enzyme reduces biopterin back to the functioning cofactor 6-tetrahydrobiopterin. The absence of MSRA indicates deficient methionine sulphoxide repair in the cytosol, meanwhile the presence of MSRB is helpful to protect the nucleus. Taken together, we have identified H2O2-mediated stress in piebald skin with distinct differences to vitiligo.
authors.affiliation: Institute for Pigmentary Disorders in association with EM Arndt University of Greifswald, Germany.
authors.forename: Tayyebeh
authors.initials: T
authors.lastname: Vafaee
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rokos
authors.forename: Mohamed M A E L
authors.initials: MM
authors.lastname: Salem
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
mesh_terms: D000328:Adult; D001706:Biopsy; D002374:Catalase / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D008840:Microfilament Proteins; D018384:Oxidative Stress / Q000502:physiology*; D016116:Piebaldism / Q000378:metabolism* / Q000473:pathology; D011621:Pteridines / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014820:Vitiligo / Q000378:metabolism / Q000473:pathology
chemical_list: D008840:Microfilament Proteins; D011621:Pteridines; D014157:Transcription Factors; D008715:Methionine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; C120376:MSRB2 protein, human; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase; C013111:methionine sulfoxide