Co-regulation of melanin precursors and tyrosinase in human pigment cells: roles of cysteine and glutathione.

Détails

ID Serval
serval:BIB_2AFCBD5CD1CB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Co-regulation of melanin precursors and tyrosinase in human pigment cells: roles of cysteine and glutathione.
Périodique
Cellular and Molecular Biology
Auteur(s)
Benathan M., Virador V., Furumura M., Kobayashi N., Panizzon R.G., Hearing V.J.
ISSN
0145-5680
Statut éditorial
Publié
Date de publication
11/1999
Peer-reviewed
Oui
Volume
45
Numéro
7
Pages
981-990
Langue
anglais
Notes
Publication types: Journal Article - Publication Status: ppublish
Résumé
Glutathione (GSH) and cysteine (CysH) have both been implicated in the biogenesis of the pheomelanin precursor 5-S-cysteinyldopa (5-S-CD). However, recent studies have shown that only CysH is transported across the membrane of isolated melanosomes, and that the positive regulation of CysH in pigment cells leads to an increased production of 5-S-CD. In the present study, the question was examined as to whether melanin precursors and tyrosinase could be coregulated by cellular thiols. To address this issue, the levels of CysH and GSH were varied in normal melanocytes and melanoma cells using buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis. Treatment with 50-100 microM BSO decreased GSH levels to less than 10% of control, and increased CysH levels between two- and five-fold in both cell types. Concomitant with this, an increase in the ratio of 5-S-CD to DOPA and a decrease in the pigment content of the cells were observed. The decrease in cell pigmentation was associated with strong decreases in tyrosine hydroxylase activity and 14C-melanin production. Only melanoma cells showed a modified tyrosinase isozyme pattern on Western immunoblots in response to BSO, while the mRNA expression of tyrosinase and TRP-1 were unchanged in both cell types. These results suggest that the balance between CysH and GSH, which is partly determined by the rate of utilization of CysH for GSH biosynthesis, regulates not only the levels of 5-S-CD and DOPA but also the melanogenic activity of pigment cells. Since DOPA functions as a cofactor in the monophenolase reaction of tyrosinase, it is proposed that the ratio of 5-S-CD to DOPA may be an important factor in the regulation of tyrosinase activity in situ.
Mots-clé
Buthionine Sulfoximine, Cells, Cultured, Cysteine, Cysteinyldopa, Dihydroxyphenylalanine, Glutathione, Humans, Infant, Newborn, Male, Melanins, Melanocytes, Melanoma, Melanosomes, Monophenol Monooxygenase, Neoplasm Proteins, Skin Neoplasms, Tumor Cells, Cultured, Tyrosine
Pubmed
Web of science
Création de la notice
25/01/2008 16:55
Dernière modification de la notice
20/08/2019 13:10
Données d'usage