| Co-Investigator(Kenkyū-buntansha) |
WAKAMATSU Kazumasa Fujita Health University, School of Health Sciences, Professor, 衛生学部, 教授 (80131259)
HIROBE Tomohisa Radiation Hazards Research Group, National Institute of Radiological Sciences, Team Leader, 放射線障害研究グループ, チームリーダー (10111238)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Murine pink-eyed dilution (p/p) melanocytes are known to possess numerous mitochondria. Melanoblasts and melanocytes increased in number in a medium supplemented with Caspase-9 inhibitor or Bax inhibitor. Caspase-9 and Bax are known to regulate the apoptosis that is related to mitochondria. These results suggest the possibility that the proliferation of pink-eyed dilution melanoblasts and melanocytes is regulated by the mechanisms related to apoptosis. The proliferative activity of murine slaty (slt/slt) melanocytes was similar to that of wild-type melanocytes, whereas the differentiation of melanocytes was greatly inhibited in slaty mice. The morphology of slaty melanosomes was also abnormal. Activities of tyrosinase and tyrosinase-related protein (TRP)-2 in slaty melanocytes were lower than in wild-type melanocytes. The content of the eumelanin was reduced, while the content of the pheomelanin was similar to that of wild-type melanocytes. These results suggest that the slaty mutation
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affects eumelanin synthesis and controls the differentiation of melanocytes via the regulation of activities of tyrosinase and TRP-2.
The eumelanin contents in the epidermis and dermis of recessive yellow (e/e) mice were much lower than those of wild-type mice, whereas the pheomelanin contents were much greater than wild-type mice. The eumelanin content in recessive yellow hairs was much lower than in wild-type hairs, whereas the pheomelanin content was much greater than in wild-type hairs. It is surprising that the eumelanin and pheomelanin contents in female hairs of recessive yellow mice were greater than in male hairs. The e gene may affect eumelanin and pheomelanin contents in hairs by influencing through sex-related mechanisms. The agouti (A/A) gene was expressed in the dermis of 0.5-,3.5- and 5.5-day-old mice, but not in the epidermis. These results suggest the pheomelanin production in the epidermis of agouti mice may be induced by the expression of the agouti gene in the dermis.
we measured contents of eumelanin (EM) and pheomelanin (PM)(chemical phenotype) in 60 primary human melanocyte cultures (51 neonatal and 9 adult), and correlated some of these values with the respective activity and protein levels of tyrosinase, and the melanocortin-1 receptor (MC1R) genotype. Melanocytes were classified into 4 types (c, c+, b-, b+) as depicted by visual pigmentation using light microscopy, and by the pigmentary phenotype of the donor's skin. There were large differences in total melanin (TM) and EM, which increased progressively for c, c+, b-, and b+ melanocytes. TM contents, the sum of EM and PM, showed good correlations with TM measured spectrophotometrically, and with the activities and protein levels of tyrosinase, but not with MC1R genotype. We conclude that 1)cultured human melanocytes vary tremendously in pigmentation, 2)EM, not PM, consistently correlates with the visual phenotype, 3)in adult melanocyte cultures, TM and EM correlate well with the ethnic background of the donors (African American>Indian>Caucasian in TM and EM), 4)MC1R loss-of-function mutations do not necessarily alter the pigmentary phenotype. Less
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