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KMID : 0370220130570060388
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Yakhak Hoeji
2013 Volume.57 No. 6 p.388 ~ p.393
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Role of Nitric Oxide 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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Previously, we have reported that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, increased melanin synthesis through intracellular Ca2+ release in B16 cells. In this study we investigated the possible involvement of nitric oxide (NO) in the mechanism of lovastatin-induced melanogenesis. Lovastatin elevated NO formation in a dose-dependent manner. Treatment with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), precursors of cholesterol, did not significantly alter the lovastatin-induced NO production, suggesting that inhibition of cholesterol metabolism may not be involved in the mechanism of this action of lovastatin. Both NO formation and melanogenesis induced by lovastatin was significantly suppressed by treatment with NG-nitro-L-arginine methyl ester (L-NAME) and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide (cPTIO), an inhibitor of NO synthase and a NO scavenger, respectively. The lovastatin-induced NO production was significantly affected not by EGTA, an extracellular Ca2+ chelator, but by an intracellular Ca2+ chelator (BAPTA/AM) and intracellular Ca2+ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular Ca2+ release in B16 cells. These results further suggest that lovastatin may be a good candidate for the therapeutic application of various hypopigmentation disorders.
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KEYWORD
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lovastatin, melanogenesis, nitric oxide, Ca2+ signal, hypopigmentation, B16 melanoma cell
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