ERK及AP-1对二氧化硅上调人肺上皮细胞纤溶酶原激活物抑制因子-1表达的作用  

Silicon dioxide-upregulated plasminogen activators inhibitor-1 protein expression is dependent on activation of extracellular signal-regulated kinase/activator protein-1 signaling pathway

作　　者：李翔[1] 胡永斌[1] 彭劲武[1] 何琼琼[1] 蒋海鹰[1] 

机构地区：[1]中南大学基础医学院病理学系,长沙410013

出　　处：《中华劳动卫生职业病杂志》2008年第7期387-390,共4页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金项目（30700661）

摘　　要：目的探讨细胞外信号调控激酶（ERK），激活蛋白（AP-1）信号通路在二氧化硅诱导人肺上皮细胞（A549）纤溶酶原激活物抑制因子-1（PAI-1）表达中的作用。方法以人肺上皮细胞A549为研究对象，200μg／ml二氧化硅刺激0～24h。干预实验采用姜黄素预处理以及c-Jun显性负性突变体（TAM67）瞬时转染阻断AP-1活性；PD98059预处理阻断ERK活性。以Western印迹检测ERK激酶活力、PAI-1蛋白表达，EMSA检测AP-1DNA结合活性。结果（1）SiO2作用A549细胞4、8、16h，AP-1DNA结合活性分别为对照的1．3、1．3、2．1倍，差异有统计学意义（P〈0．05）；10、25、50μmol／L浓度姜黄素对二氧化硅诱导的PAI-1蛋自表达抑制率分别为20％、63％、65％，差异有统计学意义（P〈0．05）；TAM-67对二氧化硅诱导的PAI-1蛋白表达的抑制率为59％，与二氧化硅刺激组比，差异有统计学意义（P〈0．05）。（2）：二氧化硅作用A549细胞诱导ERK激酶活化；PD98059对二氧化硅诱导的PAI-1蛋白表达的抑制率为51％，与二氧化硅刺激组比较，差异有统计学意义（P〈0．05）。（3）PD98059对二氧化硅诱导的AP-1DNA结合活性的抑制率为73％，与二氧化硅刺激组比较，差异有统计学意义（P〈0．05）。结论ERK／AP-1信号通路参与调控SiO2诱导的人肺上皮细胞PAI-1蛋向表达。Objective To investigate the role of extracellular signal-regulated kinase（ ERK）/activator protein-1 （AP-1） signaling pathway in SiO2-induced plasminogen aclivators inhibitor-1 （PAI-1） protein expression in human lung epithelial cells A549. Methods A549 cells were cultured and then stimulated with 200 p,g/ml SiO2 for 0-24 h. To prevent AP-1 activity,Curcumin was added into culture medium before incubated with SiO2 and transient TAM-67 tranfection was performed. In addition,PD98059 was pretreated with cells to prevent ERK activity. The PAI-1 protein expression and ERK activily were evaluated by Western blot. The AP- 1 DNA binding activily was lested by EMSA. Results （ 1 ）At 4,8 and 16 h after exposure to SiO2,the fold change of AP-1 DNA binding aclivity （relative to the control group） were1.3,1.3,and 2.1, respectively （P〈 0.05 ）. 10,25,50 μmol/L Curcumin inhibited SiO2-induced PAl- l protein expression （ inhibition ratio ： 20%, 63%, 65% ：P〈0.05 ）. TAM-67 downregulated SiO2-induced PAI-1 protein expression（ inhibition ratio：59%, P〈 0.05 ）, （2）SIO2 activated ERK and PD98059 downregulaled SiO2-induced PAI-1 protein expression （inhibition ratio：51% ,P〈0.05 ）. （3）PD98059 downregulated SiO2-induced AP-1 DNA binding activity （inhibition ratio：73%,P〈0.05）. Conclusion ERK/AP-1 signaling pathway is responsible for SiO2-induced PAI-1 pro- tein expression.

关 键 词：二氧化硅 纤溶酶原激活物抑制物1 转录因子AP-1 上皮细胞 

分 类 号：R131[医药卫生—劳动卫生]