| Project/Area Number |
15603009
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
細胞死(アポトーシス)
|
|---|
| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
|---|
Principal Investigator |
TAKAHASHI Mayumi Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research associate, 福祉振興財団・東京都老人総合研究所, 助手 (50133632)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SHIRASAWA Takuji Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, department director, 福祉振興財団・東京都老人総合研究所, 参事研究員 (80226323)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | clk-1 gene / apoptosis / mitochondria / CoQ / ultradian rhythm / Tet-offシステム / 長寿関連遺伝子 |
|---|
| Research Abstract |
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.
|
