title: Butyrylcholinesterase is present in the human epidermis and is regulated by H2O2: more evidence for oxidative stress in vitiligo.
abstract: The human epidermis holds the capacity for autocrine cholinergic signal transduction, but the presence of butyrylcholinesterase (BchE) has not been shown so far. Our results demonstrate that this compartment transcribes a functional BchE. Its activity is even higher compared to acetylcholinesterase (AchE). Moreover, we show that BchE is subject to regulation by H(2)O(2) in a concentration-dependent manner as it was recently described for AchE. Epidermal BchE protein expression and enzyme activities are severely affected by H(2)O(2) in vitiligo as previously demonstrated for AchE. Removal/reduction of H(2)O(2) by a pseudocatalase PC-KUS yields normal/increased protein expression and activities. H(2)O(2)-mediated oxidation of methionine residues in BchE was confirmed by FT-Raman spectroscopy. Computer simulation supported major alteration of the enzyme active site and its tetramerisation domain suggesting deactivation of the enzyme due to H(2)O(2)-mediated oxidation. Based on our results we conclude that H(2)O(2) is a major player in the regulation of the cholinergic signal via both AchE and BchE and this signal is severely affected in the epidermis of patients with active vitiligo.
authors.affiliation: Clinical and Experimental Dermatology/Department of Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK. K.Schallreuter@bradford.ac.uk <K.Schallreuter@bradford.ac.uk>
authors.forename: Karin U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: Nicholas C J
authors.initials: NC
authors.lastname: Gibbons
authors.forename: Carsten
authors.initials: C
authors.lastname: Zothner
authors.forename: Souna M
authors.initials: SM
authors.lastname: Elwary
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rokos
authors.forename: John M
authors.initials: JM
authors.lastname: Wood
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003198:Computer Simulation; D004817:Epidermis / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D015603:Keratinocytes / Q000201:enzymology; D008544:Melanocytes / Q000201:enzymology; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D008958:Models, Molecular; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics; D013454:Sulfoxides / Q000378:metabolism; D014820:Vitiligo / Q000378:metabolism* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D013454:Sulfoxides; D008715:Methionine; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase