酪氨酸磷酸酯酶抑制剂对tau蛋白磷酸化作用的研究  

Effects of tyrosine phosphatase inhibitor on tau phosphorylation in vivo

作　　者：周新文[1] 吴惠亮[1] 曹伟丽[1] 马丽娟[1] 王建枝[1] 

机构地区：[1]华中科技大学同济医学院基础医学院,湖北武汉430030

出　　处：《中国病理生理杂志》2004年第7期1134-1137,共4页Chinese Journal of Pathophysiology

基　　金：国家杰出青年科学基金资助项目 (No .3992 5 0 12 ) ;国家自然科学基金资助项目 (No .30 170 2 2 1)

摘　　要：目的 :探讨受体酪氨酸磷酸酯酶对大鼠海马tau蛋白磷酸化的影响。方法 :大鼠海马直接注射酪氨酸磷酸酯酶 (PTP)抑制剂钒酸钠 (PVN)或糖原合酶激酶 (GSK - 3)抑制剂氯化锂 (LiCl) ,2 4h后用免疫印迹和免疫组织化学方法检测大鼠海马tau蛋白磷酸化水平。结果 :PVN可以明显降低大鼠海马tau蛋白PHF - 1位点磷酸化水平 ,且比LiCl的作用强 (P <0 0 1) ,与LiCl联用使非磷酸化位点tau - 1明显增强 (P <0 0 5 ) ,总tau蛋白 (R111d)含量显著降低 (P <0 0 5 )。结论 :PTP抑制剂明显降低大鼠海马tau蛋白磷酸化 ,其机制可能与GSK - 3失活有关。AIM: To explore the effect of receptor tyrosine kinase system mediated by phosphotyrosine phosphatase (PTP) on tau phosphorylation in rat hippocampus. METHODS: Pervanadate (PVN), inhibitor of PTP or inhibitor of glycogen synthase kinase-3 (GSK-3), LiCl were injected into rat hippocampus by stereotaxy technique. The level of tau phosphorylation was detected by Western blot and immunohistochemistry after 24 h of injection. RESULTS: PVN significantly inhibited tau phosphorylation at PHF-1 epitope and the inhibition of tau phosphorylation by PVN was stronger than that of LiCl (P<0.01),and tau-1 epitope non-phosphorylated tau increased significantly in LiCl+PVN group than in control group (P<0.05). The level of total tau determined by R111d was significantly lower in PVN and LiCl+PVN treated groups (P<0.05) than that in LiCl and control groups. CONCLUSION: Tyrosine phosphatase inhibitor inhibited tau phosphorylation of hippocampus in rats. The underlie mechanism might be at least partially through the inhibition of GSK-3. [

关 键 词：蛋白质酪氨酸磷酸酶 TAU蛋白质类 磷酰化 

分 类 号：R363[医药卫生—病理学]