Analysis of expression regulation of selenoproteins in neurons and Gliazellen

神经元和胶质细胞硒蛋白表达调控分析

• 批准号: 5241178
• 负责人: Privatdozent Dr. Nicolai Savaskan
• 金额: --
• 依托单位: Abteilung für Anatomie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5241178?language=en
• 关键词: Analysis; expression; regulation; selenoproteins; neurons

Free radicals and oxidative stress-induced neuronal cell death has been shown to play an important role in a variety of neurological disorders such as ischemia or Alzheimer's disease. For this reason, the study of neuroprotective mechanisms is of primary interest in basic and clinical neuroscience. Beside its strong expression in muscle tissue of several species, Selenoprotein W (Se-W) is also expressed in the rat CNS. By in situ hybridization we could show that the highest transcriptional activity of this gene is located to the hippocampal cornu ammonis. Previous findings that Se-W is associated with glutathione (GSH) suggest a possible role for this protein in oxidation/reduction catalysis and thus make it a candidate for a neuroprotective facotr. Our aim is to investigate - by in situ hybridization and immunohistochemistry - the anatomical distribution of Se-W on a cellular level in the rat brain. Further colocalization of Se-W expression with cell-type specific immunological markers will be performed to identify the subtypes of CNS cells expressing the gene. Overexpression of the cloned Se-W cDNA in neuronal and microglial cell-lines is performed to analyze the possible protective properties of the gene product against oxidativ stress.

自由基和氧化应激诱导的神经元细胞死亡已被证明在多种神经系统疾病如缺血或阿尔茨海默病中发挥重要作用。由于这个原因，神经保护机制的研究是基础和临床神经科学的主要兴趣。硒蛋白W （seloprotein W, Se-W）除了在几种动物的肌肉组织中强烈表达外，还在大鼠中枢神经系统中表达。通过原位杂交，我们可以证明该基因的最高转录活性位于海马角氨。先前的研究发现Se-W与谷胱甘肽（GSH）相关，表明该蛋白在氧化/还原催化中可能起作用，因此使其成为神经保护因子的候选物。我们的目的是通过原位杂交和免疫组织化学研究硒- w在大鼠脑细胞水平上的解剖分布。进一步将Se-W表达与细胞类型特异性免疫标记物共定位，以鉴定表达该基因的中枢神经系统细胞亚型。将克隆的Se-W cDNA在神经元和小胶质细胞系中过表达，以分析该基因产物对氧化应激的可能保护特性。