期刊
EXPERIMENTAL DERMATOLOGY
卷 20, 期 9, 页码 761-763出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1600-0625.2011.01296.x
关键词
antimelanogenic activity; cAMP-responsive element binding protein; manassantin A; microphthalmia-associated transcription factor; tyrosinase
类别
资金
- Priority Research Center Program [2010-0029709]
- NRF of Korea [2009-0066803]
Microphthalmia-associated transcription factor (MITE) is inducible in response to cAMP through the cAMP-responsive element-binding protein (CREB) and plays a pivotal role in the melanocyte-specific expression of tyrosinase or tyrosinase-related proteins (TRPs) for melanin biosynthesis. Manassantin A from Saururus chinensis inhibits cAMP-induced melanin production in B16 melanoma cells. Here, we focused on molecular basis of the antimelanogenic activity. Manassantin A consistently inhibited the cAMP elevator 3-isobutyl-1-methylxanthine (IBMX)- or dibutyryl cAMP-induced melanin production in B16 cells or in melan-a melanocytes by down-regulating the expression of tyrosinase or TRP1 gene. Moreover, manassantin A suppressed MITF induction through IBMX-activated CREB pathway, directly inhibiting the Ser-133 phosphorylation of CREB. However, manassantin A did not affect IBMX-increased cAMP levels in these cells but also other cAMP-dependent melanogenic pathways through post-translational modifications of MITF. This putative molecular mechanism of manassantin A in the inhibition of melanin production suggests its pharmacological potential in skin hyperpigmentation.
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