PMID- 23629861 OWN - NLM STAT- MEDLINE DCOM- 20131216 LR - 20231213 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 27 IP - 8 DP - 2013 Aug TI - Basic evidence for epidermal H2O2/ONOO(-)-mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS. PG - 3113-22 LID - 10.1096/fj.12-226779 [doi] AB - Nonsegmental vitiligo (NSV) is characterized by loss of inherited skin color. The cause of the disease is still unknown despite accumulating in vivo and in vitro evidence of massive epidermal oxidative stress via H2O2 and peroxynitrite (ONOO(-)) in affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Strictly segmental vitiligo (SSV) with dermatomal distribution is a rare entity, often associated with stable outcome. Recently, it was documented that this form can be associated with NSV (mixed vitiligo). We here asked the question whether ROS and possibly ONOO(-) could be players in the pathogenesis of SSV. Our in situ results demonstrate for the first time epidermal biopterin accumulation together with significantly decreased epidermal catalase, thioredoxin/thioreoxin reductase, and MSRA/MSRB expression. Moreover, we show epidermal ONOO(-) accumulation. In vivo FT-Raman spectroscopy reveals the presence of H2O2, methionine sulfoxide, and tryptophan metabolites; i.e., N-formylkynurenine and kynurenine, implying Fenton chemistry in the cascade (n=10). Validation of the basic data stems from successful repigmentation of skin and eyelashes in affected individuals, regardless of SSV or segmental vitiligo in association with NSV after reduction of epidermal H2O2 (n=5). Taken together, our contribution strongly supports H2O2/ONOO-mediated stress in the pathogenesis of SSV. Our findings offer new treatment intervention for lost skin and hair color. FAU - Schallreuter, Karin U AU - Schallreuter KU AD - Institute for Pigmentary Disorders, E. M. Arndt University, Greifswald, Germany. k.schallreuter@bradford.ac.uk FAU - Salem, Mohammed A E L AU - Salem MA FAU - Holtz, Sarah AU - Holtz S FAU - Panske, A AU - Panske A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130429 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Nitrates) RN - 14691-52-2 (Peroxynitrous Acid) RN - 0 (Biopterins) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.11.1.- (pseudocatalase) RN - EC 1.11.1.6 (Catalase) SB - IM MH - Adolescent MH - Adult MH - Biopterins/metabolism MH - Catalase/*metabolism/therapeutic use MH - Child MH - Child, Preschool MH - Enzyme Activation/radiation effects MH - Epidermis/metabolism/pathology MH - Eyelashes/drug effects/*metabolism/pathology MH - Female MH - Humans MH - Hydrogen Peroxide/*metabolism MH - Infant MH - Male MH - Middle Aged MH - Nitrates/metabolism MH - Oxidation-Reduction/drug effects MH - Peroxynitrous Acid/*metabolism MH - Skin/drug effects/*metabolism/pathology MH - Skin Pigmentation/drug effects MH - Spectrum Analysis, Raman MH - Ultraviolet Rays MH - Vitiligo/drug therapy/*metabolism/pathology MH - Young Adult OTO - NOTNLM OT - FT-Raman spectroscopy OT - MSRA OT - MSRB OT - RNS OT - ROS OT - thioredoxin reductase EDAT- 2013/05/01 06:00 MHDA- 2013/12/18 06:00 CRDT- 2013/05/01 06:00 PHST- 2013/05/01 06:00 [entrez] PHST- 2013/05/01 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] AID - fj.12-226779 [pii] AID - 10.1096/fj.12-226779 [doi] PST - ppublish SO - FASEB J. 2013 Aug;27(8):3113-22. doi: 10.1096/fj.12-226779. Epub 2013 Apr 29.