权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Studies on the specific pathway of energy metabolism held in tumor cells and their application on the development of anti-tumor drugs

肿瘤细胞能量代谢特定途径的研究及其在抗肿瘤药物开发中的应用

基本信息

批准号：
07557164
负责人：
TERADA Hiroshi
金额：
$ 9.66万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557164/
关键词：
hexokinase tumor cells anti-tumor drugs energy metabolism mitochondri ミトコンドリア解糖系阻害剤

项目摘要

Previously, we found that type II hexokinase is predominantly expressed in malignant tumor cells synchronized with the expression of type 1 glucose transporter and concluded the possible formation of atypical pathway of energy metabolism in tumor cells. In this research project, we focused on this atypical pathway of energy metabolism, we tried to characterize it and to develop new anti-tumor drugs. The obtained findings are follows :1) we isolated and characterized the promoter region of the gene encoding type II hexokinase (ref.1)2) we examined the effects of various culture couditions on the steady state transcript level of type II hexokinase and found a possible regulation of the transcript level of this enzyme by oxygen concentration (not yet published)3) to clarify the structural and functional features of this enzyme, we developed several chimera proteins between type II and type IV enzymes, and characterized their fouctional features (ref.4)4) to know the functional features of mitochondria-bound hexokinase, we isolated tumor mitochondria and examined the preference of the membrane bound hexokinase for ATP molecules synthesized by various systems. As a result, mitochondria-bound hexokinase was found to use preferentially the ATP synthesized by oxidative phosphorylation (ref.4)

在此之前，我们发现II型己糖激酶主要在恶性肿瘤细胞中表达，与1型葡萄糖转运蛋白的表达同步，并得出结论，在肿瘤细胞中可能形成非典型的能量代谢途径。在本研究项目中，我们专注于这种非典型的能量代谢途径，试图对其进行表征并开发新的抗肿瘤药物。获得的结果如下：1）我们分离并表征了编码II型己糖激酶的基因的启动子区（参考文献1）2）我们研究了不同培养条件对II型己糖激酶稳态转录水平的影响，发现氧浓度可能调节该酶的转录水平（尚未发表）3）为了阐明该酶的结构和功能特征，我们开发了几种II型和IV型酶之间的嵌合蛋白，并表征了它们的功能特征（参考文献4）4）为了了解结合于葡聚糖的己糖激酶的功能特征，我们分离了肿瘤线粒体，并检测了膜结合的己糖激酶对各种系统合成的ATP分子的偏好。结果发现，结合于葡聚糖的己糖激酶优先利用氧化磷酸化合成的ATP（参考文献4）。