The key target of neuroprotection after the onset of ischemic stroke: secretory pathway Ca(2+)-ATPase 1.
The key target of neuroprotection after the onset of ischemic stroke: secretory pathway Ca(2+)-ATPase 1.
复制标题
缺血性脑卒中发病后神经保护的关键靶点：分泌途径Ca(2)-ATPase 1。
DOI：
10.4103/1673-5374.162760
复制
发表时间：
2015-08
影响因子：
6.1
通讯作者：
Hu ZP
中科院分区：
文献类型：
--
作者：
Li LH;Tian XR;Hu ZP
心肌梗死后细胞内Ca ~（2+）超载的调节机制涉及分泌途径Ca ~（2+）-ATP酶1和高尔基体，并已被充分理解。然而，高尔基体在脑缺血再灌注后钙超载中的作用尚不清楚。采用四血管闭塞大鼠作为脑缺血动物模型。免疫印迹法检测皮质和海马分泌途径Ca ~（2+）-ATP酶1的表达，并测定胞浆和高尔基体中Ca ~（2+）浓度。结果表明，在缺血和再灌注过程中细胞质Ca 2+超载，再灌注后达到高峰。高尔基体Ca 2+水平表现出相反的效果。大脑皮层和海马高尔基体特异性分泌途径Ca ~（2+）-ATP酶1的表达在缺血和再灌注前均降低，再灌注6 h后升高。这种变化类似于分离的高尔基体囊泡中钙离子的变化。这些结果表明，高尔基体参与了钙超载的形成和缓解，分泌途径Ca ~（2+）-ATPase 1密切响应于神经细胞的缺血和再灌注。因此，我们得出结论，分泌途径Ca 2 +-ATP酶1在胞浆钙调节中起着重要作用，其表达可用作高尔基体应激的标志物，对脑缺血和再灌注作出反应。分泌途径Ca ~（2+）-ATP酶1可能是缺血性脑卒中重要的神经保护靶点。
The regulatory mechanisms of cytoplasmic Ca2+ after myocardial infarction-induced Ca2+ overload involve secretory pathway Ca2+-ATPase 1 and the Golgi apparatus and are well understood. However, the effect of Golgi apparatus on Ca2+ overload after cerebral ischemia and reperfusion remains unclear. Four-vessel occlusion rats were used as animal models of cerebral ischemia. The expression of secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus was detected by immunoblotting, and Ca2+ concentrations in the cytoplasm and Golgi vesicles were determined. Results showed an overload of cytoplasmic Ca2+ during ischemia and reperfusion that reached a peak after reperfusion. Levels of Golgi Ca2+ showed an opposite effect. The expression of Golgi-specific secretory pathway Ca2+-ATPase 1 in the cortex and hippocampus decreased before ischemia and reperfusion, and increased after reperfusion for 6 hours. This variation was similar to the alteration of calcium in separated Golgi vesicles. These results indicate that the Golgi apparatus participates in the formation and alleviation of calcium overload, and that secretory pathway Ca2+-ATPase 1 tightly responds to ischemia and reperfusion in nerve cells. Thus, we concluded that secretory pathway Ca2+-ATPase 1 plays an essential role in cytosolic calcium regulation and its expression can be used as a marker of Golgi stress, responding to cerebral ischemia and reperfusion. The secretory pathway Ca2+-ATPase 1 can be an important neuroprotective target of ischemic stroke.