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Elucidation of the Interaction between Nutrition and the Gene Expression Control System Based on "Omics" Analyses

基于“组学”分析阐明营养与基因表达控制系统之间的相互作用

基本信息

批准号：
15380090
负责人：
KATO Hisanori
金额：
$ 10.11万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

To extend the transcriptomic analysis of the effect of dietary protein, the effect of protein nutrition on the gene expression profile of adipose tissue was examined. The up-regulation of the PPARγ gene was thought to be involved in the elevated sensitivity to insulin under protein malnutrition. Additionally, function analysis of some animal proteins was carried out by using a DNA microarray. Then the effect of amino acid deprivation on transcriptome and proteome of a hepatoma cell line was analyzed. Many genes were found to directly respond to amino acids; they included the genes for some transcription factors and translation factors. We then explored the application of omics approach to the toxic effect of the excess of an amino acid. The result indicated that, in the case of cystine excess, the liver and heart are major targets of its toxic effect. The regulatory mechanisms of transcription and translation by amino acids were then examined in detail. Transcription factors such as Foxos and ATFs turned out to play important roles. The mechanism whereby amino acids regulate the signaling pathway of insulin was studied in light of a mediating factor, IRS-1. We could propose a novel regulatory mechanism of cell signaling in which amino acids serves as regulators of some phosphatases.Moreover, to explore a new direction of omics analyses in nutrigenomics area, we attempted to use transcriptomics for the evaluation of the safety of food. The safety of hypoallergenic wheat flour was confirmed with this technique, showing the effectiveness of this approach. It seemed to be essential to build a nutrigenomics database for efficient development of nutrigenomics area. A unique database was created and publicized. Raw data of DNA microarray analyses and publication information on nutrigenomics experiments are being accumulated.

为了扩展蛋白质影响的转录分析，研究了蛋白质营养对脂肪组织基因表达谱的影响。PPARγ基因的上调被认为与蛋白质营养不良引起的胰岛素敏感性升高有关。此外，还利用DNA微阵列对一些动物蛋白进行了功能分析。然后分析了氨基酸剥夺对肝癌细胞系转录组和蛋白质组的影响。许多基因被发现直接对氨基酸作出反应，其中包括一些转录因子和翻译因子的基因。然后，我们探索了组学方法在过量氨基酸的毒性效应中的应用。结果表明，在胱氨酸过量的情况下，肝脏和心脏是其毒性作用的主要目标。然后详细研究了氨基酸对转录和翻译的调控机制。事实证明，FOXOS和ATF等转录因子发挥了重要作用。根据一种中介因子IRS-1，研究了氨基酸调节胰岛素信号通路的机制。我们可以提出一种新的细胞信号调节机制，其中氨基酸是一些磷酸酶的调节者。此外，为了探索营养基因组学领域组学分析的新方向，我们尝试利用转录组学来评价食品的安全性。用该技术证实了低过敏性小麦粉的安全性，表明了该方法的有效性。为了有效地发展营养基因组学领域，建立营养基因组学数据库似乎是必不可少的。创建并公布了一个独特的数据库。DNA微阵列分析的原始数据和营养基因组学实验的出版信息正在积累中。