Eumelanin Biosynthesis Is Regulated by Coordinate Expression of Tyrosinase and Tyrosinase-Related Protein-1 Genes

Kuzumaki, Takejiro; Matsuda, Ayako; Wakamatsu, Kazumasa; Ito, Shosuke; Ishikawa, Kiichi

doi:10.1006/excr.1993.1159

Cited by 78 publications

(42 citation statements)

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“…Melanogenesis, a major differentiated function of melanocytes, plays an important role in protecting skin from sun-related injuries and is principally responsible for skin color. [1][2][3][4] Tyrosinase plays a critical regulatory role in melanin biosynthesis and it is suggested that tyrosinase activity is pivotal. 2,23) Thus numerous studies have focused on characterizing the melanogenic pathways that regulate tyrosinase activity in melanocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Melanin biosynthesis proceeds through a complex series of enzymatic and chemical reactions in melanocytes. [1][2][3][4] Synthesis of melanin starts from the conversion of amino acid L-tyrosine to 3,4-dihydroxyphenylalanine (L-dopa) and then the oxidation of L-dopa yields dopaquinone by tyrosinase, an enzyme catalyzing the ratelimiting step for melanin biosynthesis.…”

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confidence: 99%

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Inhibitory Effect of Miconazole on Melanogenesis

Mun

Lee

Jeong

et al. 2004

Biological & Pharmaceutical Bulletin

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Miconazole (MIC), a regional antifungal agent, has been used worldwide in the treatment of superficial mycosis. However, the effect of MIC on skin pigmentation is not known. In this study, we investigated the inhibitory effect of MIC on melanogenesis in B16 melanoma cells. Tyrosinase activity and melanin content were dose dependently decreased by MIC as compared with untreated cells. The level of tyrosinase protein expression was reduced with treatment MIC. A decrease in cell proliferation was observed in B16 cells treated with MIC 30 m mM, indicating that the MIC-induced depigmenting effect was caused by inhibition of melanin synthesis and not by destruction of B16 cells. Furthermore, MIC markedly suppressed a a-melanocyte stimulating hormone or forskolin-induced tyrosinase activity in B16 cells. Therefore the depigmenting effect of MIC might be due to the inhibition of tyrosinase activity and tyrosinase expression, which eventually slows melanin biosynthesis. These results indicate that MIC may be a useful inhibitor of melanogenesis in B16 cells and suggest that it may have beneficial effects in the treatment of hyperpigmentation disorders such as ephelis and melasma.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Inhibitory Effect of Miconazole on Melanogenesis

Mun

Lee

Jeong

et al. 2004

Biological & Pharmaceutical Bulletin

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“…Furthermore, DNA repair inhibition was also observed in the UDS assay, where cells were arrested at G 0 /G 1 and DNA semi-conservative synthesis was minimal. Herbimycin A, a tyrosine kinase inhibitor which also modulates cis-DDP response, was found to block the G 1 /S transition of mouse ®broblasts (Kuzumaki et al, 1996), a mechanism which may lead to either more ecient repair or to apoptosis. The former is unlikely, as herbimycin A enhances cis-DDP toxicity.…”

Section: Discussionmentioning

confidence: 99%

Regulation of cellular response to cisplatin-induced DNA damage and DNA repair in cells overexpressing p185erbB-2 is dependent on the ras signaling pathway

Yen¹,

Nie²,

You³

et al. 1997

Oncogene

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We have examined the role of erbB-2 expression in the modulation of cellular toxicity to cisplatin. We have demonstrated that treatment of NIH3T3-erbB-2 cells, which overexpress the p185 erbB-2 product of the human erbB-2 gene, with a monoclonal antibody directed against the extracellular domain (TAb-250), results in enhanced cisplatin cytotoxicity. A similar enhancement was obtained when cells were exposed to herbimycin A and its analogue CP127 374, both of which inhibit tyrosine kinase activity. Using the host cell reactivation (HCR) of reporter gene expression from cisplatindamaged plasmid and unscheduled DNA synthesis (UDS) following cisplatin treatment of cells, we have found that modulation of erbB-2 by TAb-250 was associated with inhibition of DNA repair. TAb-250 alone, under conditions which modulate DNA repair, slightly reduces the S-phase of the cell cycle, while cisplatin induced arrest at S and G 2 phases. Combination of TAb-250 and cisplatin only slightly prevented cisplatin-induced S and G 2 blocks. Since the ras pathway is one of the major signaling components coupled to erbB-2, we have examined the role of ras in DNA repair regulation. Transient expression of a ras dominant negative mutant, Asn-17-ras H , prevents DNA repair modulation by TAb-250, suggesting that the erbB-2 receptor regulates DNA repair mechanism(s), at least in part, through ras-coupled pathway(s).

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“…In B16 mouse melanoma cells, melanogenesis is inhibited by the tumor promoting phorbol ester, TPA Fuller et al, 1990;Kuzumaki et al, 1993;Mahalingam et al, 1996). The mechanism by which TPA exerts its e ect remains controversial.…”

Section: Introductionmentioning

confidence: 99%

In B16 melanoma cells, the inhibition of melanogenesis by TPA results from PKC activation and diminution of microphthalmia binding to the M-box of the tyrosinase promoter

et al. 1998

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In B16 melanoma cells, cAMP-induced melanogenesis is inhibited by the tumor promoting phorbol ester, TPA. However, the role of PKC activation or depletion in the inhibition of melanogenesis by TPA remains controversial. In this report, using speci®c PKC inhibitors, we demonstrated that PKC inhibition does not impair cAMPinduced melanin synthesis and tyrosinase expression. Further, the inhibition of melanogenesis by TPA results from a decrease of the tyrosinase promoter transcriptional activity and this e ect is mimicked by over-expression of a constitutively active form of PKC a. These ®ndings clearly demonstrate that PKC activation accounts for the inhibition of melanin synthesis by TPA. Additional experiments were undertaken to elucidate the mechanism by which TPA inhibits the tyrosinase gene transcription. Deletions and mutation in the tyrosinase promoter showed that TPA acts on a M-box which is involved in tissuespeci®c expression and regulation by cAMP of the tyrosinase gene. We showed that TPA decreases the binding of microphthalmia, a basic helix ± loop ± helix transcription factor, to the M-box. Since microphthalmia, strongly stimulates the transcriptional activity of the promoter we propose that TPA, through PKC activation, decreases microphthalmia binding to the M-box of the tyrosinase promoter, thereby leading to a reduced tyrosinase expression and melanogenesis inhibition.

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Eumelanin Biosynthesis Is Regulated by Coordinate Expression of Tyrosinase and Tyrosinase-Related Protein-1 Genes

Cited by 78 publications

References 0 publications

Inhibitory Effect of Miconazole on Melanogenesis

Inhibitory Effect of Miconazole on Melanogenesis

Regulation of cellular response to cisplatin-induced DNA damage and DNA repair in cells overexpressing p185erbB-2 is dependent on the ras signaling pathway

In B16 melanoma cells, the inhibition of melanogenesis by TPA results from PKC activation and diminution of microphthalmia binding to the M-box of the tyrosinase promoter

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