title: Quinones are reduced by 6-tetrahydrobiopterin in human keratinocytes, melanocytes, and melanoma cells.
abstract: Quinones are potentially dangerous substances generated from quinols via the intermediates semiquinone and hydrogen peroxide. Low semiquinone radical concentrations are acting as radical scavengers while high concentrations produce reactive oxygen species and quinones, leading to oxidative stress, apoptosis, and/or DNA damage. Recently it was recognised that thioredoxin reductase/thioredoxin (TR/T) reduces both p- and o-quinones. In this report we examine additional reduction mechanisms for p- and o-quinones generated from hydroquinone (HQ) and coenzyme Q10 and by 17beta-estradiol by the common cofactor 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin (6BH(4)). Our results confirmed that TR reduces the p-quinone 1,4 benzoquinone and coenzyme Q10-quinone back to HQ and coenzyme Q10-quinol, respectively, while 6BH(4) has the capacity to reduce coenzyme Q10-quinone and the o-quinone produced from 17beta-estradiol. 6BH(4) is present in the cytosol and in the nucleus of epidermal melanocytes and keratinocytes as well as melanoma cells and colocalises with TR/T. Therefore we conclude that both mechanisms are major players in the prevention of quinone-mediated oxidative stress and DNA damage.
authors.affiliation: Department of Biomedical Sciences, University of Bradford, Bradford, BD7 1DP, UK. K.Schallreuter@Bradford.ac.uk
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rokos
authors.forename: Bhaven
authors.initials: B
authors.lastname: Chavan
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Gillbro
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cemeli
authors.forename: Carsten
authors.initials: C
authors.lastname: Zothner
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
authors.forename: John M
authors.initials: JM
authors.lastname: Wood
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000502:physiology; D002478:Cells, Cultured; D004249:DNA Damage; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D010084:Oxidation-Reduction; D011809:Quinones / Q000378:metabolism*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D011809:Quinones; D001708:Biopterins; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase; C003402:sapropterin