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Study on physiological function of brain-specific PNP 14

脑特异性PNP 14的生理功能研究

基本信息

批准号：
09672252
负责人：
NAKAJO Shigeo
金额：
$ 2.18万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

PNP 14 is a family protein of synucleini, which is recently thought to be responsible for Alzheimer's and Parkinson's diseases. In the present study, age-dependent changes in the expression lebel of PNP 14 in the rat brain was examined by using specific antibody and nucleotide probes. The expression of mRNA for PNP 14 was investigated by in situ hybridization and found abundantly in olfactory bulb, hippocampus, and cerebellar cortex when juvenile rats were used. Expression level of the mRNA decreased with increasing age. Although the very low expression in the brain of rat embryo was detected by Northern blot analysis, it significantly increased in that of adult rat. Immunoblot analysis of PNP 14 in the brain indicated that decrease in protein levels of PNP 14 was also found in an age-dependent manner in the same regions except in the olfactory bulb. The decrease in protein levels in the brain appears to be due to decrease in expression of the mRNA.It is thought that physiological function of PNP 14 in the rat brain might be diminished in an age-dependent manner.It was determined that l27Tyrosine residue of PNP 14 was phosphorylated in vitro bytyrosine kinases such as EGF receptors and src-kinase. Synucleini was also phosphorylated by both tyrosine kinases. These results are useful to clarify the physiological function of PNP 14 family proteins.It was shown that domain Ill of PNP 14 and a-synuclein is responsible for the binding to GAPDH.The amino acid sequence, KKE(D)X_<3-6>KXEE in domain III of both proteins may be important as target for GAPDH.Transgenic mice introducing the gene of PNP 14 and synucleini were produced. The phenotypic analysis will be investigated.

PNP 14是突触核蛋白的一个家族蛋白，最近被认为与阿尔茨海默病和帕金森病有关。本研究采用特异性抗体和核苷酸探针检测了PNP 14在大鼠脑中的表达水平随年龄的变化。通过原位杂交研究PNP - 14 mRNA的表达，发现在幼年大鼠嗅球、海马和小脑皮层中大量表达PNP - 14 mRNA。mRNA的表达水平随年龄的增加而降低。虽然Northern blot检测到大鼠胚胎脑组织中表达极低，但在成年大鼠脑组织中表达显著增加。大脑中PNP - 14的免疫印迹分析表明，除了嗅球外，PNP - 14蛋白水平在相同区域也以年龄依赖的方式下降。大脑中蛋白质水平的下降似乎是由于mRNA表达的减少。我们认为PNP - 14在大鼠脑中的生理功能可能以年龄依赖性的方式减弱。结果表明，PNP 14的l27Tyrosine残基在体外被酪氨酸激酶（如EGF受体和src激酶）磷酸化。Synucleini也被两种酪氨酸激酶磷酸化。这些结果有助于阐明PNP 14家族蛋白的生理功能。结果表明，PNP - 14和a-synuclein的结构域ii负责与GAPDH结合。两种蛋白结构域III的氨基酸序列KKE(D)X_<3-6>KXEE可能是GAPDH的重要靶点。获得了引入PNP - 14基因和突触核蛋白的转基因小鼠。表型分析将被研究。