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- Title
Cysteine Deprivation Promotes Eumelanogenesis in Human Melanoma Cells.
- Authors
del Marmol, Véronique; Ito, Shosuke; Bouchard, Brigitte; Libert, Anita; Wakamatsu, Kazumasa; Ghanem, Ghanem; Solano, Francisco
- Abstract
Melanocytic cells can produce two types of pigment, pheomelanin or eumelanin. We used two types of human melanoma cell lines to explore the regulation of pigmentation by biochemical and enzymatic studies. These two cell lines were previously designated as either pheomelanotic or of mixed type when cultured in a medium rich in cysteine. We analyzed the effects of L-cysteine depletion on melanin synthesis and the involvement of the tyrosinase-related proteins hi the production of both eumelanin and phenylalanin. Cultures were exposed to L-cysteine concentrations ranging from 206 to 2.06 μM, and the following parameters were measured: tyrosine hydroxylase activity, intracellular L-cysteine and glutathione concentrations, eumelanin and pheomelanin formation, and tyrosinase-related protein-1 and -2 mRNA levels. Extracellular L-cysteine depletion significantly increased tyrosine hydroxylase activity and promoted both eumelanogenesis and visible pigmentation in both lines. In contrast, pheomelanogenesis was increased only in the pheomelanotic cell line. Whereas eumelanogenesis was apparent upon L-cysteine depletion, tyrosinase-related protein-1 expression was not induced in the pheomelanotic cells, and tyrosinase-related protein-2 expression remained unchanged. Thus, tyrosinase-related protein-1 mRNA expression seems to be concomitant, with eumelanogenesis when the L-cysteine concentration is high, but does not appear essential for eumelanogenesis at low L-cysteine concentrations. The mechanism governing pheomelanin to eumelanin balance are dependent on L-cysteine, glutathione, and tyrosinase-related protein-1 expression, but none of these factors alone appears to be dominant in directing the synthesis of a particular type of melanin.
- Subjects
MELANOMA; GLUTATHIONE; PHENOL oxidase; MELANINS; TYROSINE; CELL lines
- Publication
Journal of Investigative Dermatology, 1996, Vol 107, Issue 5, p698
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12365591