Regulation of apoptosis through clk- 1 gene

通过clk-1基因调控细胞凋亡

• 批准号: 15603009
• 负责人: TAKAHASHI Mayumi
• 金额: $ 2.3万
• 依托单位: Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15603009/
• 关键词: clk-1 gene; apoptosis; mitochondria; CoQ; ultradian rhythm; Tet-offシステム; 長寿関連遺伝子

The biological function of clk-1 gene in the regulation of apoptosis and ultradian rhythm was analyzed in the mouse. The clk-1-deficient mouse was embryonic lethal. As many apoptotic cells were observed in the whole body of the clk-1-deficient embryos before death, the CLK-1 protein may be crucial for escape from apoptosis. To clarify the mechanism underlying the apoptosis by the clk-1deficience, we attempted to cultivate of the cells or organ from the clk-1-deficient mouse. In the cells from clk-1-deficient mouse, decline in mitochondrial membrane potential and ATP production of and release of cytochrom C from mitochondria to cytosol were induced, all characteristic to the functional deterioration of mitochondria. Since the decline in the membrane potential by exogenous CoQ10 added to culture medium, the mitochondrial dysfunction in clk-1-deficient mouse is suggested to be due to the induction of apoptosis.On the other hand, significant delay of either cell cycle progression in the embryonic cells or beating rhythm of heart or cardiac myocyte in vitro. However the delays in such ultradian rhythms were rescued by the addition of CoQ10 to the culture medium.These results suggest the clk-1 gene is crucial for the regulation of apoptosis and ultradian rhythm through the mitochondrial function.

在小鼠中分析了CLK-1基因在调节凋亡和超级节奏的调节中的生物学功能。 CLK-1缺陷小鼠是胚胎致死的。由于在死亡前在CLK-1缺陷胚胎的整个体内观察到许多凋亡细胞，因此CLK-1蛋白对于逃避凋亡至关重要。为了阐明CLK-1缺乏症凋亡的基础机制，我们试图从CLK-1缺陷小鼠中培养细胞或器官。在CLK-1缺陷小鼠的细胞中，诱导线粒体膜电位的下降和ATP产生和ATP的产生和细胞色素C从线粒体到细胞质的释放，这都是线粒体功能恶化的特征。由于外源性COQ10添加到培养基中的外源性COQ10的膜电位下降，因此认为CLK-1缺陷小鼠中的线粒体功能障碍是由于凋亡的诱导。另一方面，这两种细胞周期进展的显着延迟在体外，胚胎细胞或心脏或心脏肌细胞的节奏跳动。然而，通过向培养基中添加coq10来挽救此类超级节奏的延迟。这些结果表明，CLK-1基因对于通过线粒体功能调节细胞凋亡和超级节奏至关重要。

项目成果

Coq7/clk-1 regulates mitochondrial respiration and the generation of reactive oxygen species via coenzyme Q.

Coq7/clk-1 通过辅酶 Q 调节线粒体呼吸和活性氧的产生。

• 发表时间: 2004
• 期刊: Aging Cell 3・5
• 作者: Nakai;D.;et al.
• 通讯作者: et al.