P2Y1受体对缺血状态下星形胶质细胞产生胶质原纤维酸性蛋白与胶质细胞源性神经营养因子的影响及相关信号通路（英文）

被引：12

作者：

孙景军

刘颖

叶诸榕

机构：

[1] 复旦大学上海医学院病理学系

来源：

NeuroscienceBulletin | 2008年 / 04期

关键词：

P2Y1受体; 胶质化; 胶质原纤维酸性蛋白; 胶质细胞源性神经营养因子; PI3-K/Akt/CREB; JAK2/STAT3; Ras/ERK;

D O I：

暂无

中图分类号：

R741 [神经病学];

学科分类号：

1002 ;

摘要：

目的研究P2Y1受体对缺血时星形胶质细胞产生胶质原纤维酸性蛋白(glial fibrillary acidic protein, GFAP)及胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor, GDNF)的影响及其相关信号通路。方法分别利用右侧大脑中动脉线拴阻塞及培养细胞缺氧无营养后恢复正常培养,造成体内、外缺血再灌注模型。用免疫荧光标记、实时定量 RT-PCR、Western blotting、酶联免疫吸附试验观察 P2Y1 受体、GDNF 定位,检测 GFAP、GDNF及信号分子的表达变化。结果与单纯性缺血组比较,用选择性拮抗剂 MRS2179 阻断 P2Y1 受体后,可使体内、外星形胶质细胞产生的GFAP减少,同时使其产生GDNF增加。体外缺氧无营养并阻断P2Y1受体后:可使磷酸化蛋白激酶B(Akt)及cAMP反应元件结合蛋白(cAMP response element binding protein, CREB)升高,而使磷酸化JAK2及STAT3 (Ser727)降低;JAK2的抑制剂AG490在降低磷酸化STAT3(Ser727)的同时也降低GFAP表达水平;PI3-K的抑制剂LY294002可降低磷酸化的Akt及CREB; MEK1/2抑制剂U0126可同时降低磷酸化的JAK2、STAT3 (Ser727)、Akt及CREB。结论 P2Y1受体参与短时性缺血时星形胶质细胞GFAP及GDNF的产生过程,相关信号途径分别为JAK2/STAT3 和 PI3-K/AKT/CREB,并且两条途径存在串话。

引用

页码：231 / 243

页数：13

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