title: Methyl-beta-cyclodextrin, a specific cholesterol-binding agent, inhibits melanogenesis in human melanocytes through activation of ERK.
abstract: Cholesterol has been suggested to regulate cell differentiation. In this study, we have examined the effects of cholesterol modulation on pigmentation of skin using a treatment with methyl-beta-cyclodextrin (MbetaCD), a specific cholesterol-binding agent. Treatment with MbetaCD reduced pigmentation in human melanocyte and cultured skin. This decrease in pigmentation was related to the inhibition of the expression of tyrosinase and microphthalmia-associated transcription factor of melanocytes. Stimulation of melanocytes with MbetaCD led to the time-dependent phosphorylation of extracellular signal-regulated kinase (ERK). Furthermore, ERK functionally regulated the MbetaCD-induced melanin formation in melanocytes; a ERK inhibitor, PD98059, almost completely attenuated the MbetaCD-mediated inhibition of melanin synthesis and down-regulation of MITF and tyrosinase expression. These results suggest that cholesterol reduction by MbetaCD inhibit melanin synthesis via ERK activation and subsequent MITF downregulation.
authors.affiliation: Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Jin
authors.forename: Young Yi
authors.initials: YY
authors.lastname: Lee
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kang
mesh_terms: D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000032:analysis; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology; D012880:Skin Pigmentation / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D005419:Flavonoids; C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D010455:Peptides; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D002784:Cholesterol; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one