title: Arenarol isolated from a marine sponge abrogates endothelin-1-stimulated melanogenesis by interrupting MEK phosphorylation in normal human melanocytes.
abstract: Using B16 melanoma cells for screening, we found that a marine sponge extract has a potent anti-pigmenting effect and identified arenarol as its major active compound. In normal human melanocytes (NHMs), arenarol significantly abrogated the endothelin 1 (EDN1) stimulated expression of tyrosinase, tyrosinase-related protein 1 and dopachrome tautomerase at the transcriptional, translational and enzymatic activity (only for tyrosinase) levels. That effect was accompanied by the attenuation of the increased expression level of microphthalmia-associated transcription factor (MITF) protein at the transcriptional and translational levels. Analysis of EDN1 signaling demonstrated that arenarol significantly suppressed the EDN1-induced phosphorylation of MEK, ERK, MITF and CREB but not of Raf-1s. In contrast, the forskolin-induced phosphorylation of CREB was not down-regulated by arenarol. As for the mode of action of the suppressed phosphorylation of MEK, Raf-1 activity was not directly inhibited by arenarol in vitro and pretreatment with the protein phosphatase inhibitor okadaic acid did not affect the down-regulated phosphorylation of MEK that was induced by arenarol in NHMs. The sum of these findings suggests that arenarol abrogates the EDN1-stimulated expression of melanocyte-specific proteins by interrupting MEK phosphorylation in an as yet unknown Raf-1 inactivation mechanism.
authors: Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Japan.
authors: Bong-Keun
authors: BK
authors: Choi
authors: Byung-Yoon
authors: BY
authors: Cha
authors: Takeshi
authors: T
authors: Fujiwara
authors: Akihiko
authors: A
authors: Kanamoto
authors: Je-Tae
authors: JT
authors: Woo
authors: Makoto
authors: M
authors: Ojika
authors: Genji
authors: G
authors: Imokawa
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