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β-咔啉生物碱哈尔满和哈尔醇通过 p38 丝裂原活化蛋白激酶在 B16F10 小鼠黑素瘤细胞中诱导黑色素生成。

Beta-carboline alkaloids harmaline and harmalol induce melanogenesis through p38 mitogen-activated protein kinase in B16F10 mouse melanoma cells.

机构信息

Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, Korea.

出版信息

BMB Rep. 2010 Dec;43(12):824-9. doi: 10.5483/BMBRep.2010.43.12.824.

DOI:10.5483/BMBRep.2010.43.12.824
PMID:21189160
Abstract

Melanin synthesis is regulated by melanocyte specific enzymes and related transcription factors. β-carboline alkaloids including harmaline and harmalol are widely distributed in the environment including several plant families and alcoholic beverages. Presently, melanin content and tyrosinase activity were increased in melanoma cells by harmaline and harmalol in concentration- and time-dependent manners. Increased protein levels of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2 were also evident. In addition, immunofluorescence and Western blot analyses revealed harmaline and harmalol increased cAMP response element binding protein phosphorylation and microphthalmia-associated transcription factor expression. In addition to studying the signaling that leads to melanogenesis, roles of the p38 MAPK pathways by the harmaline and harmalol were investigated. Harmaline and harmalol induced time-dependent phosphorylation of p38 MAPK. Harmaline and harmalol stimulated melanin synthesis and tyrosinase activity, as well as expression of tyrosinase and TRP-1 and TRP-2 indicating that these harmaline and harmalol induce melanogenesis through p38 MAPK signaling.

摘要

黑色素合成受黑素细胞特异性酶和相关转录因子调控。β-咔啉生物碱包括哈尔满和哈尔醇广泛存在于环境中,包括几个植物科和酒精饮料。目前,哈尔满和哈尔醇以浓度和时间依赖的方式增加黑素瘤细胞中的黑色素含量和酪氨酸酶活性。酪氨酸酶、酪氨酸酶相关蛋白-1(TRP-1)和 TRP-2 的蛋白水平也明显增加。此外,免疫荧光和 Western blot 分析显示,哈尔满和哈尔醇增加了 cAMP 反应元件结合蛋白磷酸化和小眼畸形相关转录因子的表达。除了研究导致黑色素生成的信号外,还研究了哈尔满和哈尔醇对 p38 MAPK 途径的作用。哈尔满和哈尔醇诱导 p38 MAPK 的时间依赖性磷酸化。哈尔满和哈尔醇刺激黑色素合成和酪氨酸酶活性,以及酪氨酸酶和 TRP-1 和 TRP-2 的表达,表明这些哈尔满和哈尔醇通过 p38 MAPK 信号诱导黑色素生成。

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