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KMID : 0370220150590040177
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Yakhak Hoeji
2015 Volume.59 No. 4 p.177 ~ p.183
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Role of Ca2+-activated Cl? Channels in the Stimulation of Melanin Synthesis Induced by Cyclosporin A in B16 Melanoma Cells
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Lee Yong-Soo
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Abstract
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The mechanism of melanogenesis induced by cyclosporin A (CsA) was investigated in B16 melanoma cells. CsA stimulated the production of melanin in a dose-dependent manner in the cells. In addition, CsA increased intracellular Ca2+ concentration in a dose-related fashion. Treatment with BAPTA/AM, an intracellular Ca2+ chelator significantly inhibited the CsA-induced intracellular melanin synthesis. CsA profoundly induced Cl- efflux, which was significantly blocked by niflumic acid (NFA) and flufenamic acid (FFA), specific and nonspecific inhibitors of Ca2+-activated Cl? channels (CaCCs), respectively. Furthermore, these inhibitors of CaCCs significantly inhibited the CsA-induced stimulation of melanin synthesis. Taken together, these results suggest that the activation of CaCCs may play an important role in the CsA-induced stimulation of melanin synthesis in B16 cells. These results further suggest that CaCCs may be a good target for the management of hyperpigmentation of the skin reported in the patients treated with CsA.
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KEYWORD
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cyclosporin A, melanogenesis, Ca2+ signal, Ca2+-activated Cl- channel, hyperpigmentation, B16 melanoma cell
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