1. ¹Clinical and Experimental Dermatology/Department of Biomedical Sciences, University of Bradford, Bradford, UK
2. ²Institute for Pigmentary Disorders in Association with the EM Arndt University Greifswald, Greifswald, Germany
3. ³Institute for Pigmentary Disorders in Association with the University of Bradford, Bradford, UK
4. ⁴BMFZ Charite Campus, Berlin, Germany

Correspondence: Professor Karin U. Schallreuter, Clinical and Experimental Dermatology/Department of Biomedical Sciences, University of Bradford, Bradford BD7 1DP, UK. E-mail: k.schallreuter@bradford.ac.uk

Received 4 April 2006; Revised 28 June 2006; Accepted 17 July 2006; Published online 31 August 2006.

Abstract

The human skin holds the capacity for autocrine processing of the proopiomelanocortin (POMC)-derived peptides. Recent data demonstrated the presence and functionality of ACTH, - and -melanocyte-stimulating hormone (MSH), and -endorphin in the regulation of skin pigmentation, and a role has been put forward for -MSH as an effective antioxidant. In patients with vitiligo, decreased epidermal POMC processing and low -MSH levels were documented previously. These patients accumulate hydrogen peroxide (H₂O₂) in the 10^-3 M range in their epidermis. Therefore, we examined the involvement of H₂O₂ on POMC-derived peptides as possible targets for oxidation by this reactive oxygen species. To address this, we employed immunofluorescence labelling, dot blot analysis, Fourier transform Raman spectroscopy, functionality studies, and computer simulation of the peptide structures. We demonstrate H₂O₂-mediated oxidation of epidermal ACTH, -MSH, and -endorphin in vitiligo owing to oxidation of methionine residues in the sequences of these peptides. Moreover, we show that oxidized -endorphin loses its function in the promotion of pigmentation in melanocytes. These changes are reversible upon the reduction of H₂O₂ levels by a pseudocatalase PC-KUS. Moreover, oxidation of -MSH can be prevented by the formation of a 1:1 complex with the abundant cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin. Thus, using vitiligo, we demonstrate that H₂O₂ can affect pigmentation via epidermal POMC peptide redox homeostasis.