Details

Autor(en) / Beteiligte

• Lee, J.
• Jung, E.
• Huh, S.
• Boo, Y.C.
• Hyun, C.G.
• Kim, Y-S.
• Park, D.

Titel

Mechanisms of melanogenesis inhibition by 2,5-dimethyl-4-hydroxy-3(2H)-furanone

Ist Teil von

• British journal of dermatology (1951), 2007-08, Vol.157 (2), p.242-248

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• Summary Background  Increased production and accumulation of melanin is characteristic of a large number of skin diseases, including acquired hyperpigmentation such as melasma, postinflammatory melanoderma and solar lentigo. Thus, there is a increasing need for the development of depigmenting agents. Objectives  To evaluate the depigmenting capacity of 2,5‐dimethyl‐4‐hydroxy‐3(2H)‐furanone (DMHF) and to elucidate the mechanisms by which it inhibits α‐melanocyte‐stimulating hormone (α‐MSH)‐induced melanogenesis in B16 melanoma cells in vitro. Methods  Several experiments were performed in B16 melanoma cells. We studied melanin content, tyrosinase activity and cAMP production, and performed cAMP response element (CRE) luciferase reporter assay and Western blots for proteins involved in melanogenesis. Results  The melanin content and tyrosinase activity induced by α‐MSH were inhibited significantly by DMHF. To clarify the mechanism of the depigmenting property of DMHF, we examined the involvement of DMHF in cAMP signalling induced by α‐MSH. In CRE luciferase reporter assay, CRE reporter activation induced by α‐MSH was inhibited by DMHF. Additionally, although DMHF did not inhibit cAMP production by α‐MSH, both CRE binding protein (CREB) phosphorylation and the reduction of glycogen synthase kinase‐3β phosphorylation by α‐MSH were blocked by DMHF. These data suggest that DMHF inhibits the downstream step of cAMP production induced by α‐MSH, consequently inhibiting melanogenesis. This suggestion was further confirmed by the fact that the increased production levels of microphthalmia‐associated transcription factor, tyrosinase and tyrosinase‐related protein‐1 induced by α‐MSH were all reduced by DMHF in B16 melanoma cells. Conclusions  Our study shows that DMHF inhibits α‐MSH‐induced melanogenesis by suppressing CREB phosphorylation, which is induced by protein kinase A, and suggests that DMHF may be an effective inhibitor of hyperpigmentation.