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Long-term suppression of tyrosinase by terrein via tyrosinase degradation and its decreased expression

Cited 32 time in Web of Science Cited 32 time in Scopus
Authors
Park, Seo-Hyoung; Kim, Dong-Seok; Lee, Hyun-Kyung; Kwon, Sun-Bang; Ryoo, In-Ja; Yoo, Ick-Dong; Park, Kyoung-Chan; Kim, Won-Gon; Lee, Sangku
Issue Date
2009-06
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Citation
EXPERIMENTAL DERMATOLOGY; Vol.18(6); 562-566
Keywords
melanocytemelanogenesistyrosinaseterreinproteasomal degradation
Abstract
Previously, we reported that a fungal metabolite, terrein, decreases melanin synthesis via downregulation of microphthalmia-associated transcription factor (MITF). In the present study, we further investigated the long-term hypopigmenting action of terrein in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment with terrein at a concentration of 50 mu m strongly decreased melanogenesis in a time-dependent manner. Interestingly, the decreased tyrosinase protein levels lasted for at least 7 days, even though the MITF protein levels were restored after 3 days of treatment. In accordance with the results of Western blot analyses, the tyrosinase mRNA levels were found to be continuously decreased for at least 7 days, even though recovery of the MITF mRNA levels began after 3 days of terrein treatment. Therefore, we evaluated tyrosinase downregulation to determine if it is caused by proteasomal degradation. We found that the reduction in tyrosinase levels that was induced by terrein was clearly recovered by MG-132, a proteasome inhibitor. Moreover, ubiquitination of tyrosinase increased following treatment with terrein in the presence of MG-132. Taken together, these results suggest that terrein decreases melanogenesis through ubiquitin-dependent proteasomal degradation as well as via decreased expression of its mRNA.
ISSN
0906-6705
Language
English
URI
http://hdl.handle.net/10371/78217
DOI
https://doi.org/10.1111/j.1600-0625.2009.00847.x
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College of Medicine/School of Medicine (의과대학/대학원)Dermatology (피부과학전공)Journal Papers (저널논문_피부과학전공)
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