| Project/Area Number |
15590749
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
ISHIDA Mari Hiroshima University, Research Institute for Radiation Biology and Medicine, research associate, 原爆放射線医科学研究所, 助手 (30359898)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIDA Takafumi Hiroshima University, Hospital, Instructor, 病院・講師 (40346482)
YOSHIZUMI Masao Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20282626)
MIYAGAWA Kiyoshi Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (40200133)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | DNA damage / genomic repair / atherosclerosis |
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| Research Abstract |
(1)Oxidative stress-induced DNA damage and repair in vascular smooth muscle cells.
We found that oxidative stress (H_2O_2) induced the accumulation of thymine glycol and 8-oxo-guanidine in the nucleus, by using immunocytochemical technique. With as little as 30 μM H_2O_2, thymine glycol and 8-oxo-guanidine accumulated in the nucleus 15 minutes after H_2O_2 exposure with a peak at 30 minutes. Upon this oxidative stress-induced DNA damage, DNA repair machinery, such as Rad 51 focus formation and BRCA1 accumulation, was activated. Focus formation of Rad51 did not co-localize with BRCA1 accumulation.
(2)Identification of the novel protein(s) that translocate(s) to nucleus by oxidative stress.
We found that MAP kinase integrating kinase 1 (Mnk1), which is known to be involed in eukaryotic translation, translocates to nucleus by oxidative stress. Mnk1 is phosphorylated 30 minutes after the exposure to H_2O_2, and co-localized with sc35, showing phosphorylated (activated) Mnk1 is present at the speckles. We are now analyzing the significance of Mnk1 phosphorylation and speckle localization in the nucleus.
(3)Polymorphism in genomic repair gene and cardiovascular disease.
To examine the association between polymorphism of repair gene and cardiovascular disease, genomic DNA was purified from the blood of patients with or without cardiovascular disease and polymorphism of XRCC3 gene was determined with PCR-RFLP method. About 1000 patients were agreed with the informed consent and DNA analysed. The distribution of the alleles in Japanese seems different from that in Western people. The association between polymorphism of XRCC3 and cardiovascular disease is now being analysed.
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