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http://dx.doi.org/10.17480/psk.2015.59.4.177

Role of Ca2+-activated Cl- Channels in the Stimulation of Melanin Synthesis Induced by Cyclosporin A in B16 Melanoma Cells  

Lee, Yong Soo (College of Pharmacy, Duksung Women's University)
Publication Information
YAKHAK HOEJI / v.59, no.4, 2015 , pp. 177-183 More about this Journal
Abstract
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 $Ca^{2+}$ concentration in a dose-related fashion. Treatment with BAPTA/AM, an intracellular $Ca^{2+}$ 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 $Ca^{2+}$-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.
Keywords
cyclosporin A; melanogenesis; $Ca^{2+}$ signal; $Ca^{2+}$-activated $Cl^-$ channel; hyperpigmentation; B16 melanoma cell;
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