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Kōbe-shi, Japan

Kim J.-H.,Gyeongsang National University | Sohn K.-C.,Chungnam National University | Choi T.-Y.,Chungnam National University | Kim M.Y.,Chungnam National University | And 9 more authors.
Pigment Cell and Melanoma Research

The Wnt/β-catenin signaling pathway is involved in the melanocyte differentiation and melanoma development. However, the effect of β-catenin for dendrite formation has not been clearly elucidated yet in normal human epidermal melanocytes (NHEM). To investigate the effect of β-catenin, we transduced NHEM with recombinant adenovirus expressing β-catenin. Forced expression of β-catenin led to the dramatic morphological changes of NHEM, including the reduction of dendrite length and enlargement of cell body. Concomitantly with, the protein levels for dendrite formation-related molecules, such as Rac1 and Cdc42, were markedly decreased. In addition, phosphorylation of p38 MAPK was significantly reduced by β-catenin, potentiating its inhibitory role for dendrite formation. Interestingly, overexpression of β-catenin led to the increase of protein kinase C ζ (PKCζ) level, while protein kinase C δ (PKCδ) was decreased by β-catenin, suggesting that those PKCs were β-catenin-downstream modulators in NHMC. When PKCζ was overexpressed, dendrites were shortened, with the reduced protein levels for Rac1 and Cdc42. In contrast, PKCδ overexpression led to the elongation of dendrites, with the increased levels for Rac1 and Cdc42. These results suggest that β-catenin play an inhibitory role for dendrite formation through the modulation of PKCζ and PKCδ. © 2010 John Wiley & Sons A/S. Source

Ando H.,Doshisha University | Ando H.,Kobe Skin Research Institute | Matsui M.S.,The Estee Lauder Companies Inc | Ichihashi M.,Doshisha University | Ichihashi M.,Kobe Skin Research Institute
International Journal of Molecular Sciences

Excess production of melanin or its abnormal distribution, or both, can cause irregular hyperpigmentation of the skin, leading to melasma and age spots. To date, various quasi-drugs that prevent or improve hyperpigmentary disorders have been developed and officially approved by the Ministry of Health, Labor and Welfare of Japan. Many of these inhibit the activity of tyrosinase, an enzyme required for melanin synthesis, for example, by competitive or non-competitive inhibition of its catalytic activity, by inhibiting its maturation, or by accelerating its degradation. In this review, we categorize the quasi-drugs developed in Japan to prevent or treat hyperpigmentary disorders, or both, and discuss perspectives for future development. © 2010 by the authors. Source

Mammone T.,Clinique Laboratories | Declercq L.,Estee Lauder Laboratories | Clio D.,Estee Lauder Laboratories | Corstjens H.,Estee Lauder Laboratories | And 8 more authors.
Journal of Cosmetic Dermatology

Skin hyperpigmentation, and the reactions that precipitate it, have been linked to free radicals by the fact that free radical scavengers or antioxidants can slow that hyperpigmentation. We have screened several hundred plant extracts for antioxidants and discovered one that is both a strong antioxidant and can reduce skin hyperpigmentation. Extracts of Dianella ensifolia contain 1-(2,4-dihydrophenyl)-3-(2,4-dimethoxy-3-methylphenyl) propane (DP), which was found to inhibit the free radical 1-1-diphenyl-2-picryl-hydrazyl (DPPH) with an EC 50 value of 78 μm. DP was also found to inhibit Ultraviolet (UV)C-induced lipid oxidation with an EC 50 of about 30 μm. We next investigated the effects of this antioxidant on skin hyperpigmentation. The reduction of discoloration by different topical treatments has been assessed in human volunteers using an in vivo assay for the rate of fading of UVB-induced tan. Two pharmaceutical formulas containing 4% hydroquinone (HQ) were used as positive controls, and we tested the ability of DP, a plant-derived amphoteric antioxidant, to increase performance of non-HQ cosmetic formulations. We found that the cosmetic formula containing DP produced an increase in the rate of fading compared to the two pharmaceutical treatments containing HQ. © 2010 Wiley Periodicals, Inc. Source

Ando H.,Okayama University of Science | Ando H.,Kobe Skin Research Institute | Niki Y.,Kobe Skin Research Institute | Ito M.,Niigata University | And 4 more authors.
Journal of Investigative Dermatology

Recent studies have described the role of shedding vesicles as physiological conveyers of intracellular components between neighboring cells. Here we report that melanosomes are one example of shedding vesicle cargo, but are processed by a previously unreported mechanism. Pigment globules were observed to be connected to the filopodia of melanocyte dendrites, which have previously been shown to be conduits for melanosomes. Pigment globules containing multiple melanosomes were released from various areas of the dendrites of normal human melanocytes derived from darkly pigmented skin. The globules were then captured by the microvilli of normal human keratinocytes, also derived from darkly pigmented skin, which incorporated them in a protease-activated receptor-2 (PAR-2)-dependent manner. After the pigment globules were ingested by the keratinocytes, the membrane that surrounded each melanosome cluster was gradually degraded, and the individual melanosomes then spread into the cytosol and were distributed primarily in the perinuclear area of each keratinocyte. These results suggest a melanosome transfer pathway wherein melanosomes are transferred from melanocytes to keratinocytes via the shedding vesicle system. This packaging system generates pigment globules containing multiple melanosomes in a unique manner. © 2012 The Society for Investigative Dermatology. Source

Ando H.,Doshisha University | Ando H.,Kobe Skin Research Institute | Niki Y.,Kobe Skin Research Institute | Yoshida M.,Doshisha University | And 9 more authors.
Pigment Cell and Melanoma Research

Summary There are many techniques for evaluating melanosome transfer to keratinocytes but the spectrophotometric quantification of melanosomes incorporated by keratinocyte phagocytosis has not been previously reported. Here we describe a new method that allows the spectrophotometric visualization of melanosome uptake by normal human keratinocytes in culture. Fontana-Masson staining of keratinocytes incubated with isolated melanosomes showed the accumulation of incorporated melanosomes in the perinuclear areas of keratinocytes within 48 h. Electron microscopic observations of melanosomes ingested by keratinocytes revealed that many phagosomes containing clusters of melanosomes or their fragments were localized in the perinuclear area. A known inhibitor of keratinocyte phagocytosis which inhibits protease-activated receptor-2, i.e., soybean trypsin inhibitor, decreased melanosome uptake by keratinocytes in a dose-dependent manner. These data suggest that our method is a useful model to quantitate keratinocyte phagocytosis of melanosomes visually in vitro. © 2009 John Wiley & Sons A/S. Source

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