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Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway

BACKGROUND: Melanogenesis, or the biosynthesis of melanin, plays a critical role in the pigmentation of skin, hair, and eyes. Reduced melanogenesis may lead to depigmentation conditions such as vitiligo. Psoralen, a furocoumarin derivative, is closely associated with melanogenesis, and its derivativ...

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Autores principales: Zang, Deng, Niu, Chao, Aisa, Haji Akber
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387609/
https://www.ncbi.nlm.nih.gov/pubmed/30858693
http://dx.doi.org/10.2147/DDDT.S180960
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author Zang, Deng
Niu, Chao
Aisa, Haji Akber
author_facet Zang, Deng
Niu, Chao
Aisa, Haji Akber
author_sort Zang, Deng
collection PubMed
description BACKGROUND: Melanogenesis, or the biosynthesis of melanin, plays a critical role in the pigmentation of skin, hair, and eyes. Reduced melanogenesis may lead to depigmentation conditions such as vitiligo. Psoralen, a furocoumarin derivative, is closely associated with melanogenesis, and its derivative 8-methoxypsoralen is used in psoralen and ultraviolet A therapy for pigmentation disorders. In a previous study, we synthesized a new series of amine derivatives of furocoumarin, of which 5-(morpholinomethyl)-3-phenyl-7H-furo[3,2-g]chromen-7-one (encoded as D206008) showed a remarkable melanogenic effect in B16 murine cells. METHODS: In this study, we examined the effects of D206008 on the melanogenesis-related pathways in B16 cells. D206008 increased melanin production and tyrosinase (TYR) activity, as well as the mRNA and protein expression levels of the melanogenic enzymes TYR, TRP-1 and TRP-2, and the melanogenesis-related transcription factor microphthalmia-associated transcription factor (MITF) in a dose-dependent (0–100 µM) and time-dependent (0–48 hours) manner. RESULTS: Mechanistically, D206008 inhibited β-catenin degradation by enhancing the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β), which increased the accumulation of β-catenin in the cytoplasm. Nuclear translocation of β-catenin also increased in response to D206008 treatment. CONCLUSION: Taken together, these data indicate that D206008 promotes melanin synthesis by stimulating the nuclear translocation of β-catenin, which activates MITF transcription and eventually melanogenesis.
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spelling pubmed-63876092019-03-11 Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway Zang, Deng Niu, Chao Aisa, Haji Akber Drug Des Devel Ther Original Research BACKGROUND: Melanogenesis, or the biosynthesis of melanin, plays a critical role in the pigmentation of skin, hair, and eyes. Reduced melanogenesis may lead to depigmentation conditions such as vitiligo. Psoralen, a furocoumarin derivative, is closely associated with melanogenesis, and its derivative 8-methoxypsoralen is used in psoralen and ultraviolet A therapy for pigmentation disorders. In a previous study, we synthesized a new series of amine derivatives of furocoumarin, of which 5-(morpholinomethyl)-3-phenyl-7H-furo[3,2-g]chromen-7-one (encoded as D206008) showed a remarkable melanogenic effect in B16 murine cells. METHODS: In this study, we examined the effects of D206008 on the melanogenesis-related pathways in B16 cells. D206008 increased melanin production and tyrosinase (TYR) activity, as well as the mRNA and protein expression levels of the melanogenic enzymes TYR, TRP-1 and TRP-2, and the melanogenesis-related transcription factor microphthalmia-associated transcription factor (MITF) in a dose-dependent (0–100 µM) and time-dependent (0–48 hours) manner. RESULTS: Mechanistically, D206008 inhibited β-catenin degradation by enhancing the phosphorylation of Akt and glycogen synthase kinase-3β (GSK-3β), which increased the accumulation of β-catenin in the cytoplasm. Nuclear translocation of β-catenin also increased in response to D206008 treatment. CONCLUSION: Taken together, these data indicate that D206008 promotes melanin synthesis by stimulating the nuclear translocation of β-catenin, which activates MITF transcription and eventually melanogenesis. Dove Medical Press 2019-02-12 /pmc/articles/PMC6387609/ /pubmed/30858693 http://dx.doi.org/10.2147/DDDT.S180960 Text en © 2019 Zang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Zang, Deng
Niu, Chao
Aisa, Haji Akber
Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway
title Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway
title_full Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway
title_fullStr Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway
title_full_unstemmed Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway
title_short Amine derivatives of furocoumarin induce melanogenesis by activating Akt/GSK-3β/β-catenin signal pathway
title_sort amine derivatives of furocoumarin induce melanogenesis by activating akt/gsk-3β/β-catenin signal pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387609/
https://www.ncbi.nlm.nih.gov/pubmed/30858693
http://dx.doi.org/10.2147/DDDT.S180960
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