Choi Jeong-Sun, Park Hyun-Jung, Kim Ha-Young, Kim Seong Yun, Lee Ju Eun, Choi Yun-Sik, Chun Myung-Hoon, Chung Jin-Woong, Lee Mun-Yong
Department of Anatomy, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul, 137-701, Korea.
Cell Tissue Res. 2005 Mar;319(3):359-66. doi: 10.1007/s00441-004-1033-0. Epub 2005 Jan 27.
To ascertain whether the PTEN (phosphatase and tensin homolog deleted on chromosome 10)/Akt signaling pathway is activated during ischemic brain injury, we investigated the expression and phosphorylation of PTEN and Akt by immunohistochemistry in the rat hippocampus after transient forebrain ischemia. Weak immunoreactivity for PTEN and its phosphorylated form (p-PTEN) was constitutively expressed in hippocampal neurons and astrocytes of the control rats, but their upregulation was detected mainly in reactive astrocytes in the ischemic hippocampus. Increased immunoreactivity for PTEN and p-PTEN occurred specifically in astrocytes by day 1 and was sustained for more than 2 weeks. The spatiotemporal activation of Akt in the ischemic hippocampus mirrored that of p-PTEN expression. Post-ischemic activation of Akt, revealed by phosphorylated Akt (p-Akt) immunoreactivity, was first detected at day 1 and was maintained for at least 2 weeks. Double-labeling experiments revealed that the cells expressing PTEN, p-PTEN, or p-Akt were reactive astrocytes expressing glial fibrillary acidic protein. These results demonstrate the increased phosphorylation of PTEN and Akt in reactive astrocytes of the post-ischemic hippocampus, suggesting that the PTEN/Akt pathway is involved in the astroglial reaction in the rat hippocampus after transient forebrain ischemia.
为了确定10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）/Akt信号通路在缺血性脑损伤期间是否被激活，我们通过免疫组织化学研究了短暂性前脑缺血后大鼠海马中PTEN和Akt的表达及磷酸化情况。在对照大鼠的海马神经元和星形胶质细胞中组成性表达PTEN及其磷酸化形式（p-PTEN）的弱免疫反应性，但在缺血海马中的反应性星形胶质细胞中主要检测到它们的上调。PTEN和p-PTEN的免疫反应性增加在第1天特异性地出现在星形胶质细胞中，并持续超过2周。缺血海马中Akt的时空激活与p-PTEN表达的情况相似。通过磷酸化Akt（p-Akt）免疫反应性揭示的缺血后Akt激活在第1天首次检测到，并维持至少2周。双重标记实验表明，表达PTEN、p-PTEN或p-Akt的细胞是表达胶质纤维酸性蛋白的反应性星形胶质细胞。这些结果表明缺血后海马反应性星形胶质细胞中PTEN和Akt的磷酸化增加，提示PTEN/Akt通路参与了短暂性前脑缺血后大鼠海马中的星形胶质细胞反应。
