一种新型补骨脂素衍生物BSP-1诱导B16细胞中黑色素合成的作用机制  

Mechanism of Novel Psoralen Derivatives in the Stimulation of Melanogenesis in B16 Melanoma

作　　者：庞广宪 努尔阿米乃.麦麦提 牛超[1] 阿吉艾克拜尔.艾萨 PANG Guang-Xian;Nuramina MAMAT;NIU Chao;Haji Akber AISA(Key Laboratory of Plant Resources and Chemistry of Arid Zone, State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences Urumqi 830011, China;University of Chinese Academy of Sciences, Beijing 100049, China)

机构地区：[1]中国科学院干旱区植物资源化学重点实验室新疆特有药用资源利用省部共建实验室中国科学院新疆理化技术研究所,乌鲁木齐830011 [2]中国科学院大学,北京100049

出　　处：《中国生物化学与分子生物学报》2018年第4期395-403,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：新疆维吾尔自治区自然科学基金项目(No.2017D01A76)~~

摘　　要：8-甲氧基补骨脂素(8-MOP)和5-甲氧基补骨脂素(5-MOP)等补骨脂素类药物在临床上常用于治疗白癜风,但同时具有诸多副作用。因此,发掘作用更强、毒性更小的补骨脂素类化合物用以治疗白癜风成为研究热点。在我们的前期研究中,本课题组设计合成了一系列结构新颖的补骨脂素席夫碱衍生物,并评价了它们的抗白癜风活性。本论文选取了其中一个补骨脂素席夫碱衍生物(BSP-1),研究了它对小鼠B16细胞中黑色素合成的作用及其信号通路。利用CCK法、L-Dopa氧化法、NaOH溶解法及Western印迹法分别分析BSP-1对细胞增殖、黑色素含量、酪氨酸酶(TYR)活性及相关蛋白表达的影响。结果显示,BSP-1能够促进B16细胞内黑色素生成和TYR活性,上调TYR、TRP-1、TRP-2和MITF的蛋白表达,并呈浓度依赖性。机制研究发现,BSP-1通过提高Akt和GSK-3β的磷酸化水平,上调细胞核中β-联蛋白的含量,最终使得小眼相关转录因子(MITF)的蛋白表达增加。综上所述,本研究提示BSP-1可通过调节Wnt/β-联蛋白信号通路来促进B16细胞内的黑色素合成。Psoralens such as 8-methoxypsoralen（ 8-MOP） and 5-methoxypsoralen（ 5-MOP） are clinically used in the treatment of vitiligo. However,these drugs have many side effects. Therefore,searching for a lead compound which is more effective and less toxic for the disease has become a research hot spot. A series of novel Schiff base derivatives of psoralen were designed and synthesized,then submitted to anti-vitiligo evaluation. In this research,one of these derivatives,BSP-1,was studied for its efficacy and mechanism on melanin synthesis in B16 cells. The effects of BSP-1 on cell viability,melanin content,tyrosinase（ TYR） activity and protein expression was analyzed by CCK,dissolution method,LDopa oxidation and Western blot respectively. The results showed that BSP-1 promoted melanin synthesis and TYR activity in B16 cells and up-regulated the protein expression of TYR,TRP-1,TRP-2 and MITFin a concentration-dependent manner. Molecular mechanism studies found that BSP-1 increased the protein expression of MITF by increasing the phosphorylation levels of Akt and GSK-3β and elevating the content of nuclear β-catenin. Taken together, BSP-1 promotes melanin synthesis in B16 cells by regulating the Wnt/β-catenin signaling pathway.

关 键 词：补骨脂素光化学疗法 黑色素 衍生物 信号通路 

分 类 号：Q5[生物学—生物化学] Q7