BK21PLUS R-FIND team, College of Pharmacy, Dongguk University, Seoul 100-715.
National Cancer Center, Goyang 410-769, Republic of Korea.
Biomol Ther (Seoul). 2014 May;22(3):207-12. doi: 10.4062/biomolther.2014.031.
Skin hyperpigmentation is one of the most common skin disorders caused by abnormal melanogenesis. The mechanism and key factors at play are not fully understood. Previous reports have indicated that cystamine (CTM) inhibits melanin synthesis, though its molecular mechanism in melanogenesis remains unclear. In the present study, we investigated the effect of CTM on melanin production using ELISA reader and the expression of proteins involved in melanogenesis by Western blotting, and examined the involvement of transglutaminase-2 (Tgase-2) in SK-MEL-2 human melanoma cells by gene silencing. In the results, CTM dose-dependently suppressed melanin production and dendrite extension in α-MSH-induced melanogenesis of SK-MEL-2 human melanoma cells. CTM also suppressed α-MSH-induced chemotactic migration as well as the expressions of melanogenesis factors TRP-1, TRP-2 and MITF in α-MSH-treated SK-MEL-2 cells. Meanwhile, gene silencing of Tgase-2 suppressed dendrite extension and the expressions of TRP-1 and TRP-2 in α-MSH-treated SK-MEL-2 cells. Overall, these findings suggested that CTM suppresses α-MSH-induced melanogenesis via Tgase-2 inhibition and that therefore, Tgase-2 might be a new target in hyperpigmentation disorder therapy.
皮肤色素沉着是由异常黑素生成引起的最常见的皮肤疾病之一。其机制和关键因素尚未完全阐明。先前的报告表明半胱胺(CTM)抑制黑色素合成,但其在黑素生成中的分子机制尚不清楚。在本研究中,我们使用 ELISA 读数器研究了 CTM 对黑色素生成的影响,并用 Western blot 研究了参与黑素生成的蛋白质的表达,并通过基因沉默研究了转谷氨酰胺酶-2(Tgase-2)在 SK-MEL-2 人黑素瘤细胞中的参与情况。结果表明,CTM 剂量依赖性地抑制了 SK-MEL-2 人黑素瘤细胞 α-MSH 诱导的黑素生成中的黑色素生成和树突延伸。CTM 还抑制了 α-MSH 诱导的趋化性迁移以及 α-MSH 处理的 SK-MEL-2 细胞中黑素生成因子 TRP-1、TRP-2 和 MITF 的表达。同时,Tgase-2 的基因沉默抑制了 α-MSH 处理的 SK-MEL-2 细胞中的树突延伸和 TRP-1 和 TRP-2 的表达。总的来说,这些发现表明 CTM 通过抑制 Tgase-2 抑制 α-MSH 诱导的黑素生成,因此,Tgase-2 可能成为色素沉着障碍治疗的新靶点。