Terrein: a new melanogenesis inhibitor and its mechanism

Cited 120 time in scopus
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Title
Terrein: a new melanogenesis inhibitor and its mechanism
Author(s)
S H Park; D S Kim; Won Gon KimIn Ja Ryoo; D H Lee; C H Huh; S W Youn; Ick Dong Yoo; K C Park
Bibliographic Citation
Cellular and Molecular Life Sciences, vol. 61, no. 22, pp. 2878-2885
Publication Year
2004
Abstract
Terrein is a bioactive fungal metabolite whose effects are almost unknown. In this study, we found for the first time that terrein has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 μM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrein treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrein reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.
Keyword
ERKmelanogenesisMITFterreintyrosinase
ISSN
1420-682X
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s00018-004-4341-3
Type
Article
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
Ochang Branch Institute > Anticancer Agent Research Center > 1. Journal Articles
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