Differential Expression of PTEN in Normal Adult Rat Brain and Upregulation of PTEN and p-Akt in the Ischemic Cerebral Cortex

Differential Expression of PTEN in Normal Adult Rat Brain and Upregulation of PTEN and p-Akt in the Ischemic Cerebral Cortex
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正常成年大鼠脑中 PTEN 的差异表达及缺血大脑皮层中 PTEN 和 p-Akt 的上调

DOI:
10.1002/ar.20834
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发表时间:
2009-04-01
影响因子:
2
通讯作者:
Yao, Zhong-Xiang
Yao, Zhong-Xiang
中科院分区:
医学4区
文献类型:
--
作者:
Cai, Qi-Yan;Chen, Xing-Shu;Yao, Zhong-Xiang

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肿瘤抑制因子磷酸酶和紧张素同源物(PTEN)是一种蛋白质和脂类磷酸酶。PTEN突变与大量人类癌症有关。为了了解PTEN在脑中的生理作用及其与Akt在脑缺血损伤中的关系,我们首先用免疫组织化学方法研究了PTEN在正常成年大鼠脑内的定位。然后通过Western印迹和免疫组织化学分析检测短暂性全脑缺血后PTEN和p-Akt的表达变化。我们对正常大脑的观察表明,PTEN在不同区域的胞浆、胞核和突起中分布不均。免疫组织化学结果显示,PTEN在大鼠脑内有不同程度的表达,其中嗅前核、大脑皮层、杏仁核、海马、浦肯野细胞表达最强,在基底节、丘脑、中脑、脑桥等部位也有少量表达。全脑缺血后,大脑皮层PTEN和p-Akt免疫反应增强。伴随而来的是p-Akt的核转位。双标记实验表明,PTEN和p-Akt很可能定位于神经元。这些结果表明,PTEN在正常成人脑中发挥作用,PTEN/Akt通路可能参与了缺血损伤后神经元的存活或可塑性。Anat Rec,292:498-512,2009。(C)2009年Wiley-Liss,Inc.
The tumor suppressor phosphatase and tensin homologue (PTEN) is a protein and lipid phosphatase. PTEN mutations have been associated with a large number of human cancers. To understand the physiological role of PTEN in the brain and its relationship to Akt in ischemic injury, we first investigated the localization of PTEN immunoreactivity in the brains of normal adult rats using immunohistochemistry. We then detected the modulation of PTEN and p-Akt following transient global ischemia by Western blot and immunohistochemistry analyses. Our observation of normal brains showed that PTEN was heterogeneously distributed in the cytoplasm, nuclei, and processes in different regions. It was shown immunohistochemically that PTEN was distributed differentially in rat brain, with the highest levels in the anterior olfactory nucleus, cerebral cortex, amygdaloid nucleus, hippocampus, Purkinje's cells, and several nuclei in the basal ganglia, thalamus, midbrain, and pons. After global cerebral ischemia, PTEN and p-Akt immunoreactivities were increased in the cerebral cortex. This was accompanied by the nuclear translocation of p-Akt. Double-labeling experiments revealed that PTEN and p-Akt were most likely localized to neurons. These results suggest a role for PTEN in normal adult brain and that the PTEN/Akt pathway may be involved in neuronal survival or plasticity after ischemic injury. Anat Rec, 292:498-512, 2009. (C) 2009 Wiley-Liss, Inc.