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PSD--95结构域PDZ1过表达拮抗缺氧缺糖诱导的海马神经元凋亡

胡书群, 纵艳艳, 张光毅

徐州医学院生物化学与分子生物学研究中心

摘要

为了观察突触后致密物质--95(postsynaptic density 95,PSD--95)结构域PDZ1过表达对缺氧缺糖诱导的海马神经元凋亡的影响,该研究采用培养21d的Sprague--Dawley大鼠海马神经元,加入PDZ1腺病毒颗粒感染24h,收集细胞进行免疫沉淀、免疫印迹实验;缺氧缺糖1.5h后,用DAPI染色后荧光显微镜观察细胞凋亡,并收集细胞进行免疫印迹实验。结果显示:(1)PDZ1在海马神经元中过表达;(2)过表达的PDZ1使缺氧缺糖诱导的海马神经元凋亡数量减少({sl P}<0.05);(3)过表达的PDZ1使PSD--95与GluR6结合减少;(4)PDZ1过表达抑制由缺氧缺糖诱导的大鼠海马神经元MLK3和JNK1/2磷酸化。以上结果提示,PDZ1过表达能拮抗缺氧缺糖诱导的海马神经元凋亡。

关键词： PDZ1; 缺氧缺糖; 海马神经元; 凋亡

Overexpression of PDZ1 domain of PSD--95 protein rescues hippocampl neurons from apoptosis induced by oxygen--glucose deprivation

Hu Shuqun, Zong Yanyan, Zhang Guangyi

Research Center of Biochemistry and Molecular Biology；China

Abstract

To detect the effect of PDZ1,domain of postsynaptic density 95(PSD-95),on apoptosis of hippocampal neurons induced by oxygen-glucose deprivation(OGD),Sprague-Dawley rat hippocampal neurons were infected with PDZ1-viruses after 21 days of plating.Twenty-four hours after infection,cells were treated with OGD for 1.5 h,then were incubated with DAPI and apoptosis-like cells were characterized,or were collected for co-immunoprecipitation and Western blot analyses.The results showed that:(1) PDZ1 overexpression was observed in hippocampal neurons;(2) Apoptosis induced by OGD was obviously decreased in neurons overexpressing PDZ1(P<0.05);(3) Overexpression of PDZ1 prevented the binding of GluR6 to PSD-95;(4) Overexpression of PDZ1 inhibited MLK3 and JNK1/2 activation induced by OGD.These results indicate that overexpression of PDZ1 may prevent hippocam-pal neurons from apoptosis induced by OGD.

Key words: PDZ1;oxygen-glucose deprivation;Hippocampal neurons;apoptosis

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引用本文：

胡书群, 纵艳艳, 张光毅. PSD--95结构域PDZ1过表达拮抗缺氧缺糖诱导的海马神经元凋亡[J]. 生理学报 2008; 60 (6): 730-736.

Hu Shuqun, Zong Yanyan, Zhang Guangyi. Overexpression of PDZ1 domain of PSD--95 protein rescues hippocampl neurons from apoptosis induced by oxygen--glucose deprivation. Acta Physiol Sin 2008; 60 (6): 730-736 (in Chinese with English abstract).