• Korea Journal of Cosmetic Science
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• v.1 no.1
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• pp.31-43
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• 2019

Melanosomes are specific melanin-containing intracellular organelles of epidermal melanocytes. In epidermal melanocytes, there are three kinds of key player proteins. Rab27a, melanophilin or Slac2-a and Myosin 5a form a tripartite complex connects the melanosome. Mature melanosomes make movements through the tripartite protein complex along actin filaments.In this study, we found that the haplamine (6-Methoxyflindersine) induced melanosome aggregation around the nucleus in epidermal melanocyte. In an attempt to elucidate the inhibitory effect of haplamine on melanosome transport, effect of haplamineon the expression level of Rab27a, melanophilin and Myosin 5a was measured. The results indicated that haplamine up to 5��M effectively suppressed mRNA and protein expression level of melanophilin.To determine the upstream regulator of melanophilin regulated by haplamine, we checked the level of MITF, c-JUN and USF1. Those are possible transcription factor of melanophilin. Among them,treatment of USF1 siRNA decreased mRNA and protein expression level of USF1 as well as melanophilin. Also, treatment of haplamine decreased mRNA and protein expression level of melanophilin as well as USF1 in a dose-dependent manner. Consequently, we found the inhibitory effect of haplamine on melanosome transport in melan-a melanocyte. Treatment of haplamine reduced melanophilin expression level which is a key protein of melanosome transport. We identified that USF1 could be a major transcription factor of melanophilin regulated by haplamine.

• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.343-348
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• 2013

We investigated the inhibitory effects of hesperidin on melanogenesis. To find melanosome transport inhibitor from natural products, we collected the structural information of natural products from Korea Food and Drug Administration (KFDA) and performed pharmacophore-based in silico screening for Rab27A and melanophilin (MLPH). Hesperidin did not inhibit melanin production in B16F10 murine melanoma cells stimulated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}$-MSH), and also did not affect the catalytic activity of tyrosinase. But, hesperidin inhibited melanosome transport in melanocyte and showed skin lightening effect in pigmented reconstructed epidermis model. Therefore, we suggest that hesperidin is a useful inhibitor of melanosome transport and it might be applied to whitening agent.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.466-472
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• 2023

Exon skipping is an efficient technique to inhibit specific gene expression induced by a short-sequence peptide nucleic acid (PNA). To date, there has been no study on the effects of PNA on skin pigmentation. In melanocytes, the tripartite complex is responsible for the transport of mature melanosomes from the nucleus to the dendrites. The tripartite complex is composed of Rab27a, Mlph (Melanophilin), and Myosin Va. Defects in the protein Mlph, a melanosome transport-related protein, are known to cause hypopigmentation. Our study shows that Olipass peptide nucleic acid (OPNA), a cell membrane-permeable PNA, targets exon skipping in the Mlph SHD domain, which is involved in Rab27a binding. Our findings demonstrate that OPNA induced exon skipping in melan-a cells, resulting in shortened Mlph mRNA, reduced Mlph protein levels, and melanosome aggregation, as observed by microscopy. Therefore, OPNA inhibits the expression of Mlph by inducing exon skipping within the gene. These results suggest that OPNA, which targets Mlph, may be a potential new whitening agent to inhibit melanosome movement.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.46 no.1
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• pp.11-22
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• 2020

In this study, we investigated anti-pigmentation effect of a hexapeptide. The peptide significantly reduced melanin contents and inhibited tyrosinase activity in a dose-dependent manner, in which tyrosinase is a key enzyme in melanogenesis. The peptide also significantly reduced the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and their upstream transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, the peptide suppressed the phosphorylation level of cAMP-response element binding protein (CREB), a transcription factor of MITF, and increased the phosphorylation level of extracellular signal-regulated kinase (ERK), a kinase mediates MITF phosphorylation and proteasomal degradation. The peptide significantly inhibited the expression of Rab27A, Melanophilin, and MyosinVa, the components of motor complex involved in intracellular movement of melanosome. These results suggest that Hexapeptide could be used as an effective whitening agent that has inhibitory effect on melanin production and melanosome transport by regulating expression and degradation of MITF in melanocytes.

• Journal of Life Science
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• v.32 no.5
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• pp.355-361
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• 2022

Melanin pigments are the main cause of skin color. They are produced in melanocytes and then transferred to keratinocytes, which eventually gives the skin surface a variety of colors. Although many skin-lightening or depigmenting agents have been developed, the demand for materials to reduce pig- mentation is still increasing. Here, we tried to find materials for skin-lightening or depigmentation using natural compounds and found that mistletoe (Viscum album var. coloratum) extracts (ME) had an inhibitory effect on tyrosinase activity. As a result, ME significantly reduced pigmentation in human primary melanocytes. In addition, a promoter reporter assay revealed that ME inhibited the transcription of microphthalmia-associated transcription factor (MITF), melanophilin (MLPH), tyrosinase-related protein-2 (TRP-2), and tyrosinase (TYR) genes in HM3KO melanoma cells. In addition, ME decreased the protein level for pigmentation-related molecules, such as TYR and TRP-1. Furthermore, it markedly inhibited the melanogenesis of zebrafish embryos, an in vivo evaluation model for pigmentation. To elucidate the action mechanism of ME, we investigated its effects on intracellular signaling. Eventually, the ME dramatically decreased the phosphorylation of the cAMP responsive element binding protein (CREB), AKT, and ERK. The data suggest that ME may inhibit the melanogenesis pathway by regulating the signaling pathway related to pigmentation. Taken together, these data propose that ME can be developed as a depigmenting or skin-lightening agent.