HIV1Tat抑制EAAT2表达参与HIV相关神经认知紊发生的分子机制.docx

关键词：EAAT一2；AEG．1；HIV．1 关键词：EAAT一2；AEG．1；HIV．1Tat；HAND 万方数据 AbstractThe Abstract The apoptosis of neuron is considered to be one of the key factors for the genesis of HAND．While the excessive concentration of excitatory glutamic acid in the intercellular substance induced by the decreased expression of EAAT一2 in the membrane of astrocyte is regarded as one of the important reasons for neuron apoptosis．However，the precise reason of the decreased expression of EAAT一2 remains unknown．Therefore，we attempted to illuminate the exact molecular mechanism of the decreased EAAT一2 during HAND at tissue and cell levels．In the early experiment，we discovered through immunohistochemical staining experiment that the expression of EAAT一2 was apparently decreased in the cerebral cortex of rhesus in the SHIV infection group compared with the control groups．In addition，in regions with decreased EAAT一2 expression，the number of neuron apoptosis increased correspondingly．Furthermore，we found that the expression of AEG一1 increased in the cerebral cortex of SHIV infected rhesus，and the positive cells of AEG·1 was negatively correlated with positive of EAAT一2，as was shown in statistical analysis．We discovered through experiment that the expression of AEG-1 at mRNA and protein levels were notably increased after treating the cells with HIV一1 Tat，while that of the corresponding EAAT一2 was remarkably reduced at mRNA and protein levels．We over-expressed AEG-1 in U87 cells，we found that the expression of EAAT-2 was decreased．But，when we knocked down AEG-1 in U87 cells，we found that the expression of EAAT一2 was increased；The expression of AEG-1 was negatively correlated with that of EAAT-2，as was shown in statistical analysis．So we speculated that HIV一1 Tat might down—regulate the expression of EAAT一2 through increasing AEG-1．Next，we further studied the relevant signal pathways involved in the process．Firstly，we over-expressed HIV-1 Tat and inhibited P13--K pathway together would result in obvio