Molecular characterization of the tumor specific energy metabolisms

肿瘤特异性能量代谢的分子表征

• 批准号: 08457609
• 负责人: TERADA Hiroshi
• 金额: $ 5.5万
• 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 (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457609/
• 关键词: tumor cells; energy metabolism; hexokinase; mitochondria; glycolysis; HIF; glucose transporter; 抗がん剤

To understand the tumor specific energy metabolisms in a molecular level, we carried out the following studies.1) know the molecular mechanisms of the transcriptional activation of type II hexokinase gene during carcinogenesis, we analyzed its transcript level under various conditions. As a result, the transcript levels both of HKII and GLUT1 were found to be markedly elevated by low concentration of oxygen. Involvements oftranscriptional factor HIF in the induction of many low oxygen inducible genes are reported. Now we are studying the possible involvement of HIF in the transcriptional control of HKII and GLUT1 during carcinogenesis.2) to understand the enzyme characteristics of HKII,we made and characte-rized various recombinant proteins. As a result, we succeeded to identify the region which confer sensitivity for glucose-6-phosphate.3) to understand the physiological meanings of the binding of HKII to mitochondria, we studied the chracteristics of the mt-bound HKII.As a result, binding of HKII to the mitochondrial membrane was found to be very important in the regulatiou of cross talk between oxidative phosphorylation and glycolysis.

为了在分子水平上了解肿瘤特异性能量代谢，我们进行了以下研究。1)了解II型己糖激酶基因在癌变过程中转录激活的分子机制，分析其在不同条件下的转录水平。结果发现HKII和GLUT1的转录水平在低氧浓度下显著升高。转录因子HIF参与了许多低氧诱导基因的诱导。现在我们正在研究HIF在癌变过程中参与HKII和GLUT1转录控制的可能性。2)为了了解HKII的酶特性，我们制作了各种重组蛋白并对其进行了表征。结果，我们成功地确定了赋予葡萄糖-6-磷酸敏感性的区域。3)为了了解HKII与线粒体结合的生理意义，我们研究了mt结合的HKII的特性。因此，我们发现HKII与线粒体膜的结合在氧化磷酸化和糖酵解之间的串扰调节中非常重要。

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