Changes in the proliferation and differentiation of neonatal mouse pink-eyed dilution melanocytes in the presence of excess tyrosine.
Changes in the proliferation and differentiation of epidermal melanocytes derived from newborn mice wild-type at the pink-eyed dilution (p) locus (P/P) and from congenic mice mutant at that locus (p/p) were investigated in serum-free primary culture, with or without the addition of L-Tyr. Incubation with added L-Tyr inhibited the proliferation of P/P melanocytes in a concentration-dependent manner and inhibition was gradually augmented as the donor mice aged. In contrast, L-Tyr stimulated the proliferation of p/p melanoblasts-melanocytes derived from 0.5-day-old mice, but inhibited their proliferation when derived from 3.5- or 7.5-day-old mice. L-Tyr stimulated the differentiation of P/P melanocytes. However, almost all cells were undifferentiated melanoblasts in control cultures derived from 0.5-, 3.5- and 7.5-day-old p/p mice, but L-Tyr induced their differentiation as the age of the donor mice advanced. The content of the eumelanin marker, pyrrole-2,3,5-tricarboxylic acid as well as the pheomelanin marker, 4-amino-3-hydroxyphenylalanine in p/p melanocytes was greatly reduced compared with P/P melanocytes. However, the contents of eumelanin and its precursor, 5,6-dihydroxyindole-2-carboxylic acid, as well as the contents of pheomelanin and its precursor, 5-S-cysteinyldopa in culture media from p/p melanocytes were similar to those of P/P melanocytes at all ages tested. L-Tyr increased the content of eumelanin and pheomelanin two- to threefold in cultured cells and media derived from 0.5-, 3.5- and 7.5-day-old mice. These results suggest that the proliferation of p/p melanoblasts-melanocytes is stimulated by L-Tyr, and that the differentiation of melanocytes is induced by L-Tyr as the age of the donor mice advanced, although eumelanin and pheomelanin fail to accumulate in p/p melanocytes and are released from them at all ages of skin development.
Hirobe
Tomohisa
T
Radiation Hazards Research Group, National Institute of Radiological Sciences, Anagawa, Inage-ku, Chiba, Japan. thirobe@nirs.go.jp
Wakamatsu
Kazumasa
K
Ito
Shosuke
S
D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000737:chemistry; D003548:Cysteinyldopa / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D020297:Mice, Congenic; D008822:Mice, Transgenic; D009154:Mutation; D011758:Pyrroles / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D007211:Indoles; D008543:Melanins; D011758:Pyrroles; C018362:pheomelanin; C041877:eumelanin; D003548:Cysteinyldopa; D014443:Tyrosine; C030692:5,6-dihydroxy-2-indolylcarboxylic acid; C071227:4-amino-3-hydroxyphenylalanine; C071226:pyrrole-2,3,5-tricarboxylic acid