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AVP(4-8)调控基因的新途径研究及大鼠CCTβ在昆虫细胞中的表达

【作者】 徐侃彦

【导师】 杜雨苍;

【作者基本信息】 中国科学院研究生院(上海生命科学研究院) , 生物化学与分子生物学, 2002, 博士

【摘要】 第一部分、AVP4-8调控基因的新途径AVP4-8是精氨酸加压素在脑内的天然酶解产物,具有促进学习记忆的功能,它能在大鼠脑内引起一系列生理生化反应,RT-PCR结合Southern杂交结果表明,AVP4-8能提高大鼠海马神经元内CTP:磷酸胆碱胞苷转移酶(CCT)的mRNA水平,以及大鼠海马胶质细胞中c-fos的mRNA水平。其拮抗剂ZDC(C)PR能够抑制这一作用。用放线菌素D中止细胞mRNA合成后发现,AVP4-8能提高CCT mRNA和c-fos mRNA的稳定性。这提示转录后水平的调控是AVP4-8影响一些基因mRNA水平的重要手段。此外,AVP4-8上调海马神经元内CCT mRNA水平导致了其胞内CCT酶活性的上升,从而进一步证明AVP4-8的某些功能是通过与CCT相关的途径来完成的。

【Abstract】 Part1. The New Pathways by Which AVP4-8 Regulate GenesXu Kanyan ( Biochemistry )Directed by Prof. Du YucangThe neuropeptide AVP4-8 is a metabolite of argipressin which has been shown to have potent memory-enhancing activity. It can evoke a series of biophysical and biochemical events in rat brain. Using RT-PCR plus Southern Blot, we found that AVP4-8 could upregulate the mRNA level of CTP: phosphocholine cytidylyltransferase in rat hippocampal neurons and the mRNA level of c-fos in rat hippocampal astrocytes. It’s antagonist, ZDC(C)PR could inhibit the process. Using Actinomycin-D to inhibit the cell’s transcription, we found AVP4-8 could prolong the halflife of CCT mRNA and c-fos mRNA, which suggesting the role of posttranscriptional regulation in AVP4-8’s effect on some genes’ mRNA levels.We also found the upregulation of CCT mRNA led to the increase of enzymatic activity, this further proved the speculation that CCT may play an<WP=4>important role in some of the AVP4-8 ’s functions.

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