姜黄素通过上调SOCS表达抑制JAK2/STAT信号通路的机制  

Curcumin inhibits JAK2/STAT signaling through increasing the expression of SOCS in myeloproliferative neoplasms

作　　者：邢冲云[1] 周琳 庄强[1] 汤丽苑[1] 

机构地区：[1]温州医科大学附属第一医院血液科,浙江温州325015

出　　处：《温州医科大学学报》2015年第10期718-722,共5页Journal of Wenzhou Medical University

基　　金：温州市科技局科研基金资助项目(Y20130044)

摘　　要：目的:研究姜黄素在骨髓增殖性肿瘤(MPNs)中通过调节细胞因子信号转导抑制蛋白1、3(SOCS1、SOCS3)表达抑制JAK2/STAT信号通路的机制。方法:体外培养HEL及32D细胞株,分别用40μmol/L姜黄素处理24、48 h。通过Western blot法检测JAK2/STAT信号通路及SOCS1、SOCS3蛋白表达水平;通过染色体免疫共沉淀法检测组蛋白乙酰化程度改变;通过比色法检测组蛋白去乙酰化酶(HDAC)活性。结果:体外实验表明姜黄素显著抑制HEL及32D细胞JAK2/STAT信号通路。姜黄素能够抑制HDAC活性,同时降低HDAC1、HDAC3和HDAC8表达。姜黄素通过抑制HDAC活性,进而增强SOCS1、SOCS3启动子组蛋白乙酰化程度,从而上调SOCS1、SOCS3 m RNA及蛋白表达水平。结论:姜黄素通过上调SOCS1、SOCS3表达水平抑制JAK2/STAT信号通路。作为一个相对无毒的天然小分子化合物,姜黄素联合其他抑制JAK2/STAT信号通路的药物可能有助于MPNs的临床治疗。Objective： To investigate the mechanism of curcumin in inhibiting JAK2/STAT signaling through increasing the expression of SOCS1/3 in myeloproliferative neoplasms. Methods： JAK2/STAT signaling and protein levels of SOCS1/3 were detected by Western blotting in HEL and 32 D. Acetylation of histone in the regions of SOCS1/3 promoter was detected by immunoprecipitation assay. Furthermore, HDAC enzyme activity was detected by colorimetric HDAC activity assay kit. Results： Curcumin inhibited JAK2/STAT signaling in HEL and 32 D cells in vitro. Curcumin could inhibite HDAC enzyme activities and decreased the levels of HDAC1, 3 and 8. Curcumin elevated the m RNA and protein levels of SOCS1/3 via triggering acetylation of histone in the regions of SOCS1/3 promoter. Conclusion： Taken together, our data uncover a regulatory mechanism of SOCS1/3 through inhibition of HDAC activity by curcumin.

关 键 词：姜黄素 骨髓增殖性肿瘤 组蛋白去乙酰化酶 细胞因子信号转导抑制蛋白 

分 类 号：R96[医药卫生—药理学]