Butyrylcholinesterase is present in the human epidermis and is regulated by H2O2: more evidence for oxidative stress in vitiligo.
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.
Schallreuter
Karin U
KU
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>
Gibbons
Nicholas C J
NC
Zothner
Carsten
C
Elwary
Souna M
SM
Rokos
Hartmut
H
Wood
John M
JM
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
D012333:RNA, Messenger; D013454:Sulfoxides; D008715:Methionine; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase