B16 흑색종세포에서 로바스타틴에 의한 멜라닌 합성 촉진효과에 미치는세포내 칼슘의 역할

Role of Intracellular Ca 2+ in the Lovastatin-Induced Stimulation of Melanin Synthesis in B16 Melanoma Cells

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 inves- tigated the possible involvement of intracellular Ca 2+ 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. Treat- ment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced mel- anin 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 dem- onstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular Ca 2+ concentration in a dose- related fashion. Treatment with EGTA, an xtracellular Ca 2+ chelator did not significantly alter the lovastatin-induced intra- cellular Ca 2+ increase and melanin synthesis, whereas intracellular Ca 2+ reduction with BAPTA/AM and intracellular Ca 2+ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results sug- gest that the tracellular Ca 2+ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. hese results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.