摘要
探讨胰岛素缺乏的糖尿病大鼠皮层糖原合酶激酶-3(GSK-3)及蛋白磷酯酶-2A(PP-2A)变化及其对tau蛋白磷酸化的作用.用链脲佐菌素(streptozotocin,STZ)建立胰岛素缺乏的糖尿病大鼠模型,用放射性配体结合实验检测了GSK-3和PP-2A的活性,蛋白质印迹检测了tau蛋白的磷酸化水平及PP-2A的表达.结果提示:在糖尿病大鼠皮层,GSK-3活性升高,PP-2A活性及表达降低,tau蛋白在Ser198/Ser199/Ser202和Ser396/Ser404位点磷酸化.应用GSK-3的选择性抑制剂Li2CO3后,GSK-3活性降低,PP-2A活性及表达恢复,tau蛋白在Ser198/Ser199/Ser202和Ser396/Ser404位点磷酸化水平降低.研究提示:糖尿病大鼠皮层GSK-3升高可能抑制PP-2A的活性,升高的GSK-3和降低的PP-2A协同促进tau蛋白的磷酸化.
The changes of glycogen synthase kinase-3 （GSK-3） and protein phosphatase-2A （PP-2A）, and the role of them in the regulation of the abnormally hyperphosphorylated some sites of tau in the cortex of diabetic rat were investigated. The diabetic rat model was induced by streptozotocin. The activities of GSK-3, PP-2A were measured by liquid scintillation for incorporated radioactivity in control, DM, DM ＋ Li2CO3 groups. The level of hyperphosphorylated tau and the expression of ^2PP-2A was measured respectively by Western blot. It is suggested that GSK-3 activity increases, PP-2A activity and expression decrease, and hyperphosphorylated tau be produced at Ser198/Ser199/Ser202 and Ser396/Ser404 in DM rats cortex. After the DM rat were treated with Li2CO3, the inhibition of GSK-3 activity and the improvement of PP-2A activity were found, and hyperphosphorylation of tau at Ser198/Ser199/Ser202 and Ser396/Ser404 were deduced. These studies firstly suggested that an increase of GSK-3 activity might inhibit PP-2A activity, and which produce hyperphosphorylated of tau at Ser198/Ser199/Ser202 and Ser396/Ser404 in DM rat cortex in common.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2006年第8期789-794,共6页
Progress In Biochemistry and Biophysics
