DOI | Trouver le DOI : https://doi.org/10.1096/fj.11-201897 |
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Auteur | Rechercher : Schallreuter, K.U.; Rechercher : Salem, M.A.E.L.; Rechercher : Gibbons, N.C.J.; Rechercher : Maitland, D.J.; Rechercher : Marsch, E.; Rechercher : Elwary, S.M.A.1; Rechercher : Healey, A.R. |
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Affiliation | - Conseil national de recherches du Canada. Institut de recherche en biotechnologie du CNRC
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Format | Texte, Article |
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Sujet | aromatic hydrocarbon receptor; cyclooxygenase 2; cytochrome P450 1A1; hydrogen peroxide; indoleamine 2,3 dioxygenase; peroxynitrite; reactive oxygen metabolite; tryptophan; tryptophan hydroxylase; adult; clinical article; Fenton reaction; Fourier transform mass spectrometry; immune response; in vitro study; in vivo study; mass spectrometry; Raman spectrometry; regulatory T lymphocyte; stress; vitiligo; computer simulation; epidermis; hydrogen peroxide; indoleamine-pyrrole 2,3,-dioxygenase; oxidative stress; peroxynitrous acid; receptors, aryl hydrocarbon; signal transduction; t-lymphocytes, regulatory |
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Résumé | Vitiligo is characterized by a mostly progressive loss of the inherited skin color. The cause of the disease is still unknown, despite accumulating in vivo and in vitro evidence of massive oxidative stress via hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) in the skin of affected individuals. The most favored hypothesis is based on autoimmune mechanisms. Since depletion of the essential amino acid L-tryptophan (Trp) severely affects various immune responses, we here looked at Trp metabolism and signaling in these patients. Our in vivo and in vitro data revealed total absence of epidermal Trp hydroxylase activities and the presence of H 2O2/ONOO- deactivated indoleamine 2,3-dioxygenase. Aryl hydrocarbon receptor signaling is severely impaired despite the ligand (Trp dimer) being formed, as shown by mass spectrometry. Loss of this signal is supported by the absence of downstream signals (COX-2 and CYP1A1) as well as regulatory T-lymphocytes and by computer modeling. In vivo Fourier transform Raman spectroscopy confirmed the presence of Trp metabolites together with H2O2 supporting deprivation of the epidermal Trp pool by Fenton chemistry. Taken together, our data support a long-expressed role for in loco redox balance and a distinct immune response. These insights could open novel treatment strategies for this disease. © FASEB. |
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Date de publication | 2012 |
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Dans | |
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Langue | anglais |
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Publications évaluées par des pairs | Oui |
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Numéro NPARC | 21269455 |
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Exporter la notice | Exporter en format RIS |
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Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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Identificateur de l’enregistrement | e5ac2ae4-360f-4662-856f-5520fbd07ea0 |
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Enregistrement créé | 2013-12-12 |
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Enregistrement modifié | 2020-04-21 |
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