BBB Seminar: Karin U. Schallreuter
From the bench to the bedside – In vivo and in vitro evidence for ROS/RNS-mediated stress in vitiligo
Karin U. Schallreuter
Centre for Skin Sciences, University of Bradford, UK
Vitiligo is a disabling skin disorder where affected individuals lose their inherited skin colour. The world wide prevalence ranges from 0.5-1.5%. Men and women are affected equally. The cause of this ancient disease is yet unknown. To date there is accumulating in vitro and in vivo evidence for the involvement of massive hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) generation and accumulation in the skin of these individuals. In fact in acute disease epidermal concentrations in 10-3M range have been shown by in vivo FT-Raman spectroscopy. This oxidative/nitrative stress affects many signals and pathways including the entire antioxidants machinery, 6-/7-tetrahydrobiopterin (6BH4/7BH4) synthesis and recycling as well as 6BH4 driven tryptophan, phenylalanine and tyrosine turnover. Moreover, reactive oxygen species (ROS)/reactive nitrogen species (RNS) affect the cholinergic and adrenergic system and pro-opiomelanocortin (POMC)-signalling. Surprisingly these patients have no increased risk of solar induced skin cancer despite the fact that they have increased DNA damage even in the plasma, as evidenced by the presence of 8-hydroxyguanine (8-OHG). At the present time this paradox is explained by constant up-regulation of wild-type functioning p53 tumour suppressor protein in association with increased MDM2p76 regulator of p53. The development and application of a topical active pseudocatalase PC-KUS formulation leads to stabilisation of active disease and to repigmentation of the lost skin colour.
Host: Aurora Martinez, Department of Biomedicine