지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록· 키워드
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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 $Ca^{2+}$ 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 $N^G$-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 $Ca^{2+}$ chelator, but by an intracellular $Ca^{2+}$ chelator (BAPTA/AM) and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular $Ca^{2+}$ 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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참고문헌 (29)
참고문헌 신청
Romero-Graillet, C / 1996 / Ultraviolet B radiation acts through the nitric oxide and cGMP signal transduction pathway to stimulate melanogenesis in human melanocytes / J. Biol. Chem 271:28052
Schauer, E / 1994 / Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes / J. Clin. Invest 93:2258
Thody, A. J / 1998 / Does a-MSH have a role in regulating skin pigmentation in humans / Pigment Cell Res 11:265
Imokawa, G / 1995 / Endothelin-1 as a new melanogen: coordinated expression of its gene and the tyrosinase gene in UVB-exposed human epidermis / J. Invest. Dermatol 105:32
Nordlund, J. J / 1986 / Prostaglandin E2 and D2 but not MSH stimulate the proliferation of pigment cells in the pinnal epidermis of the DBA/2 mouse / J. Invest. Dermatol 86:433
Schauer, E / 1994 / Proopiomelanocortin-derived peptides are synthesized and released by human keratinocytes / J. Clin. Invest 93:2258
Thody, A. J / 1998 / Does a-MSH have a role in regulating skin pigmentation in humans / Pigment Cell Res 11:265
Imokawa, G / 1995 / Endothelin-1 as a new melanogen: coordinated expression of its gene and the tyrosinase gene in UVB-exposed human epidermis / J. Invest. Dermatol 105:32
Nordlund, J. J / 1986 / Prostaglandin E2 and D2 but not MSH stimulate the proliferation of pigment cells in the pinnal epidermis of the DBA/2 mouse / J. Invest. Dermatol 86:433
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