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KMID : 0370220130570010024
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Yakhak Hoeji
2013 Volume.57 No. 1 p.24 ~ p.31
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Role of Intracellular Ca2+ in the Lovastatin-Induced Stimulation of Melanin Synthesis in B16 Melanoma Cells
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Lee Yong-Soo
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Abstract
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Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular Ca2+ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin
production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin
by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular Ca2+ concentration in a doserelated fashion. Treatment with EGTA, an extracellular Ca2+ chelator did not significantly alter the lovastatin-induced intracellular Ca2+ increase and melanin synthesis, whereas intracellular Ca2+ reduction with BAPTA/AM and intracellular Ca2+ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular Ca2+ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.
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KEYWORD
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lovastatin, melanogenesis, cAMP, Ca2+ signal, hypopigmentation, B16 melanoma cell
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