Methyl-beta-cyclodextrin, a specific cholesterol-binding agent, inhibits melanogenesis in human melanocytes through activation of ERK.
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.
Jin
Sun Hee
SH
Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea.
Lee
Young Yi
YY
Kang
Hee Young
HY
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*
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