Methyl-β-cyclodextrin, a specific cholesterol-binding agent, inhibits melanogenesis in human melanocytes through activation of ERK
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- Jin, S.H., Lee, Y.Y. & Kang, H.Y. Arch Dermatol Res (2008) 300: 451. doi:10.1007/s00403-008-0864-z
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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-β-cyclodextrin (MβCD), a specific cholesterol-binding agent. Treatment with MβCD 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 MβCD led to the time-dependent phosphorylation of extracellular signal-regulated kinase (ERK). Furthermore, ERK functionally regulated the MβCD-induced melanin formation in melanocytes; a ERK inhibitor, PD98059, almost completely attenuated the MβCD-mediated inhibition of melanin synthesis and down-regulation of MITF and tyrosinase expression. These results suggest that cholesterol reduction by MβCD inhibit melanin synthesis via ERK activation and subsequent MITF downregulation.