Buthionine sulfoximine diverts the melanogenesis pathway toward the production of more soluble and degradable pigments.
Buthionine sulfoximine (BSO) is a specific inhibitor of γ-glutamylcysteine synthetase, thus blocking the synthesis of glutathione (GSH). It is known that this makes that BSO affects melanin synthesis because of the role of thiols in melanogenesis. However, BSO may also react with the intermediate oxidation products of melanogenesis, a possibility that has not been investigated from the initial steps of the pathway. We created in vitro conditions simulating eumelanogenesis (oxidation of L-DOPA in the absence of GSH) and pheomelanogenesis (oxidation of L-DOPA in the presence of GSH) under presence or absence of BSO. BSO made that eumelanogenesis results in pigments more soluble and less resistant to degradation by hydrogen peroxide than pigments obtained without BSO. A similar but less marked effect was observed for pheomelanogenesis only at subsaturating concentrations of GSH. These results suggest that BSO diverts the melanogenesis pathway toward the production of more soluble and degradable pigments.
Departamento de Ecología Evolutiva, Estación Biológica de Doñana-CSIC, C/Américo Vespucio s/n, 41092 Sevilla, Spain. Electronic address: galvan@ebd.csic.es.
Ismael
I
Galván
Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi 470-1192, Japan.
Kazumasa
K
Wakamatsu
Instituto de Investigación en Recursos Cinegéticos (IREC)-CSIC-UCLM-JCCM, Ronda de Toledo s/n, 13005 Ciudad Real, Spain.
Carlos
C
Alonso-Alvarez
Departamento de Bioquímica y Biología Molecular B e Inmunología, Facultad de Medicina, Universidad de Murcia, 30100 Murcia, Spain.
Francisco
F
Solano
D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D004151:Dipeptides / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*
D000963:Antimetabolites; D004151:Dipeptides; D008543:Melanins; D007980:Levodopa; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; C017341:gamma-glutamylcysteine
Buthionine sulfoximine; Glutathione; Hypopigmenting agents; Melanins; Melanogenesis