| Project/Area Number |
14380255
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Nagasaki University |
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Principal Investigator |
OKAICHI Kumio Nagasaki University, Graduate school of biomedical sciences, Associate professor, 大学院・医歯薬学総合研究科, 助教授 (80124874)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Yutaka Nagasaki University, Graduate school of biomedical sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (00073130)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | p53 / environmental stress / crosstalk / radiation response / signal transduction / phosphorylation / 環境ストレ |
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| Research Abstract |
We investigated the p53 signaling pathway induced by hypergravity in the human glioblastoma cell line A172. Hypergravity induced the accumulation of p53 and the phosphorylation of p53 at Ser-15. The phosphorylation of p53 with hypergravity was not inhibited by wortmannin, the P1I-kinase inhibitor. This indicated that the p53 signal pathway induced by hypergravity is different from other p53 signal pathways, such as that of the DNA damage signal. Hypergravity did not induce expression of the genes Waf-1 or Bax, located downstream from p53. We also examined the expression of genes with hypergravity using a DNA microarray containing oligo DNA from 30,000 human genes. Hypergravity did induce the expression of some genes concerned with the cell signaling pathway and cytoskeleton of the cell, but not any of the p53-downstream genes. DNA microarray revealed the induction of many genes to enable the cells to adapt to the hypergravity environment.
We investigated the p53 signal pathway by phosph
… More
orylation at serine 15 and 20, and we made mutations of p53, S15D and S20D which are mimics of phosphorylation. We introduced them in human lung adenocarcinoma cell line, H1299. The accumulation of S15D inhibited the cell growth. On the other hands, the accumulation of S20D did not inhibit the cell growth. Then, we examined the expression of genes in the cells with S15D or S20D by using the Human Oligo Chip 30K. Some genes concerned with cell signaling pathway, cell cycle or DNA replication were induced by S15D. We also examined western blotting by the Panorama Ab Micro Array (Sigma) contained 224 antibodies of cell signaling and found that the MAPK pathway was inhibited by S15D. We considered that the phosphorylation of p53 at serine 15 may inhibited cell growth by some signal pathway different from established p53 signal pathways of cell cycle. In S20D cells, CDK2 was induced and no apoptosis gene was induced, then cell cycle regulation seems to be canceled. In these cells, no stress specific induced gene was detected. This indicates that the phosphorylation of p53 does not exert only one site but co-work with several sites. Less
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