Modulation of Microphthalmia-associated Transcription Factor Gene Expression Alters Skin Pigmentation

Lin, Connie B.; Babiarz, L.; Liebel, Frank; Kizoulis, Menas; Gendimenico, Gerard J.; Seiberg, Miri; Price, Edmund; Fisher, David E.

doi:10.1046/j.1523-1747.2002.19615.x

Cited by 93 publications

(88 citation statements)

References 66 publications

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“…5) Melanin is synthesized in epidermal melanocytes, and then is transferred into epidermal keratinocytes via the melanocytes' dendrites. 6) Melanogenesis is the process by which melanin is produced (and subsequently distributed) by melanocytes within the skin and hair follicles. 7) This process results in the synthesis of melanin pigments, which plays a protective role against skin photocarsinogenesis.…”

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confidence: 99%

4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

Kim¹,

Lee

et al. 2005

Biological & Pharmaceutical Bulletin

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Tyrosinase (monophenol, dihydroxy-L-phenylalanin: oxygen oxidoreductase, EC 1.14.18.1) is a copper-dependent protein widely distributed in nature.2) The enzyme catalyzes two different reactions: the hydroxylation of monophenols to o-diphenols (monophenolase activity) and the oxidation of odiphenols to o-quinones (diphenolase activity), both utilizing molecular oxygen.3)The enzymatic browning of fruits and vegetables is mostly related to the oxidation of endogenous phenolic containing compounds catalyzed by polyphenol oxidase. 4) Tyrosinase also is responsible for melanization in animals, and is the key enzyme for the regulation of melanogenesis in mammals. 5)Melanin is synthesized in epidermal melanocytes, and then is transferred into epidermal keratinocytes via the melanocytes' dendrites. 6) Melanogenesis is the process by which melanin is produced (and subsequently distributed) by melanocytes within the skin and hair follicles.7) This process results in the synthesis of melanin pigments, which plays a protective role against skin photocarsinogenesis.8) The main physiological stimulus of melanogenesis is the ultraviolet radiation of solar light, which can act directly on melanocytes or indirectly through the release of keratinocyte-derived factors such as MSH (a-melanocyte stimulating hormone). 9)One of the biggest causative agents of hyperpigmentaion is probably UV light. 10) However, skin darkening can be suppressed, at least partially, by deactivating of tyrosinase. 11)Therefore, tyrosinase inhibitors have become increasingly important in the cosmetic and medicinal products used in the prevention of hyperpigmentaion.12) Many compounds, such as hydroquinone, 13) kojic acid, 14) and benzaldehyde-O-alkyloximes 15) have been reported as tyrosinase inhibitors. The established murine B16F10 melanoma cell (B16 cells) line offers a model system with readily quantifiable markers that are characteristic of differentiating, including melanogenesis. 16) In B16 cells, a-tocopheryl ferulate was shown to have depigmenting effect. 17) Although 4,4Ј-dihydroxybiphenyl (44Ј-BP), a bisphenol derivative was known as a radical scavenger for methacrylate polymerization, 18) but its efficacy on tyrosinase inhibition and melanin biosynthesis has not been reported.The aim of this study was to characterize inhibition mode of 44Ј-BP on mushroom tyrosinase. We also examined the inhibitory effect of 44Ј-BP on melanin biosynthesis, and cell viability in B16 cells as a biomarker for the potential cytotoxicity. Cell Culture B16 cells (from Korean Cell Line Bank) were cultured in DMEM with 10% fetal bovine serum (FBS; Gibco) and penicillin/streptomycin (100 IU/50 mg/ml) in a humidified atmosphere containing 5% CO 2 in air at 37°C. B16 cells were cultured in 24-well plates for the melanin quantification and enzyme activity assays. MATERIALS AND METHODS MaterialsDetermination of 44-BP for Cell Viability The cell proliferation assay was carried out by the method of Tada et al. using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (...

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4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

Kim¹,

Lee

et al. 2005

Biological & Pharmaceutical Bulletin

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“…The microphthalmia-associated transcription factor is implicated in melanocyte development and also upregulates melanogenesis via transactivation of tyrosinase gene expression. Lin et al (2002) showed that LA reduced the microphthalmia-associated transcription factor and tyrosinase promoter activities, resulting in depigmentation. Attention should be focused on the regulative mechanisms of LA, not only a reduction of intracellular tyrosinase expression but also direct tyrosinase inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Dihydrolipoic acid is capable of enhancing antioxidant potency by regenerating L-ascorbic acid vitamin E (Kagan et al, 1992), and reportedly impacts both the regulation of tyrosinase gene expression and direct inhibition of tyrosinase (Lin et al, 2002). Moreover, dihydrolipoic acid is considered to have superior inhibitory activity in melanin biosynthesis when compared to parent LA (Tsuji-Naito et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Ex vivo pig skin models have demonstrated that LA decreases UVB radiation-induced cell death or apoptosis (Rijnkels et al, 2003). Animal studies using dark-skinned Yucatan swine have also shown that topical treatments with LA for 8 wk suppressed hyperpigmentation of skin (Lin et al, 2002). However, there is little evidence of a link to a melaninsuppressing effect by LA in human skin cells.…”

Section: Introductionmentioning

confidence: 99%

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.ALPHA.-Lipoic Acid Inhibits Melanogenesis in Three-dimensional Human Skin Model

Unno

Ito

Sagesaka

2009

FSTR

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The overproduction of pigmentary melanin in the skin causes an undesirable cosmetic appearance. The present study was undertaken to evaluate the inhibitory effect of α-lipoic acid (LA) on melanogenesis using a three-dimensional human skin model with ultraviolet (UV) irradiation. It is evident that melanin biosynthesis in human skin cells was decreased by the treatment with LA under the concentration range from 0.01 to 0.1% (w/v) in a concentration-dependent fashion, reflecting no effect on cell viability.

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“…Tyrosinase activity was determined according to the method of Lin et al (24). B16 and A375 cells were seeded and treated as described above.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells

Alesiani

Cicconi²,

Mattei³

et al. 2009

Int J Oncol

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Abstract. In this study, the processes of differentiation and melanogenesis induced by 5,7-dimethoxycoumarin in murine (B16) and human (A375) melanoma cells were investigated.Taking into account the previously demonstrated antiproliferative and differentiation activities of this compound, we examined Ras/Raf/Mek/Erk mitogen-activated protein kinase activity following treatment; inhibition of Mek 1/2 kinase activity and subsequent reduction in Erk 1/2 activation were detected in both cell types. We observed melanogenesis induction associated to an increase in cAMP-response elementbinding protein (CREB) and microphthalmia-associated transcription factor (Mitf) expression, both involved in its regulation. Mitf is fundamental for development, survival and differentiation of melanocyte and melanoma, since it regulates transcription of genes encoding for proteins involved in cell cycle progression or in melanogenesis, such as the enzyme tyrosinase. A significant increase of tyrosinase activity was revealed following treatment in B16 but not in A375 cells, although a strong synthesis of melanin was induced by 5,7-dimethoxycoumarin in both cell lines. The treatment induced protoporphyrine IX accumulation involved in melanogenesis since it promotes stability of cAMP. Finally, the Mek 1/2 inhibitor U0126 significantly potentiated growth inhibition of B16 cells triggered by 5,7-dimethoxycoumarin, suggesting that down-regulation of Raf/Mek/Erk pathway sensitizes melanoma cells to 5,7-dimethoxycoumarin treatment.

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Modulation of Microphthalmia-associated Transcription Factor Gene Expression Alters Skin Pigmentation

Cited by 93 publications

References 66 publications

4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

.ALPHA.-Lipoic Acid Inhibits Melanogenesis in Three-dimensional Human Skin Model

Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells

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Modulation of Microphthalmia-associated Transcription Factor Gene Expression Alters Skin Pigmentation

Cited by 93 publications

References 66 publications

4,4&prime;-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

4,4&prime;-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

.ALPHA.-Lipoic Acid Inhibits Melanogenesis in Three-dimensional Human Skin Model

Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells

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4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor

4,4′-Dihydroxybiphenyl as a New Potent Tyrosinase Inhibitor