title: Down-regulation of melanin synthesis by a biphenyl derivative and its mechanism.
abstract: Down-regulation of melanin synthesis is required for recovery of pigmentary disorders and it is known that direct inhibitors of tyrosinase, the key enzyme in melanin synthesis, such as hydroquinone with a phenol structure, suppress melanin synthesis. We screened several phenolic derivatives using B16 melanoma cells and found that a biphenyl derivative, 2,2'-dihydroxy-5,5'-dipropyl-biphenyl (DDB), down-regulated melanin synthesis effectively. Although DDB has a phenol structure, it did not inhibit tyrosinase in vitro, thus we examined its mechanism in detail. Western blotting revealed that the amount of tyrosinase was decreased by DDB, and pulse-chase labeling and immunoprecipitation analysis showed a decrease of mature tyrosinase and acceleration of tyrosinase degradation in its presence. These results suggest that DDB down-regulates melanin synthesis by inhibiting the maturation of tyrosinase, leading to acceleration of tyrosinase degradation.
authors.affiliation: Basic Research Laboratory, Kanebo Ltd., Odawara, Kanagawa, Japan. knakamura@oda.cos.kanebo.co.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hideyo
authors.initials: H
authors.lastname: Uchiwa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kawa
authors.forename: Masako
authors.initials: M
authors.lastname: Mizoguchi
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000201:enzymology / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects
chemical_list: C486798:2,2'-dihydroxy-5,5'-dipropylbiphenyl; D001713:Biphenyl Compounds; D008543:Melanins; D010636:Phenols; D011500:Protein Synthesis Inhibitors; D014442:Monophenol Monooxygenase