| Project/Area Number |
16510032
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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 |
Risk sciences of radiation/Chemicals
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| Research Institution | Chiba University |
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Principal Investigator |
SUZUKI Nobuo Chiba University, Graduate School of Medicine, PROFESSOR, 大学院・医学研究院, 教授 (90111426)
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| Co-Investigator(Kenkyū-buntansha) |
KITA Kazuko Chiba University, Graduate School of Medicine, LECTURER, 大学院・医学研究院, 講師 (80302545)
SUZUKI Toshikazu Chiba University, Graduate School of Medicine, RESEARCH ASSOCIATE, 大学院・医学研究院, 助手 (70270527)
SUGAYA Shigeru Chiba University, School of Medicine, TECHNICAL OFFICIAL, 医学部, 教務職員 (90334177)
唐田 清伸 千葉大学, 大学院・医学研究院, 助手 (90345017)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | GENE MUTATION / HUMAN CELL / HUMAN SERUM / CHAPERON / UBIQUITIN-LIKE-PROTEIN / X-RAY / OXIDATIVE STRESS / HYDROPEROXIDE / DNA修復 / プロテアーゼ / 放射線 / DNA合成 / ヒドロペルオキシド |
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| Research Abstract |
We previously reported that modulation of cell mutability by human serum factors is associated with increased levels of protease activity. The present work is designed to examine the relationships between cell mutability and chaperons such as GRP78,GRP94,HSP27 and SUMO-3. : (1)GRP94 ; One of the chaperons, GRP94, was identified as a candidate gene for the mediator molecule by analysis of X-ray-induced protease. GRP94 was suggested to be involved in cellular X-ray resistance by the colony forming assay using siRNA for GRP94 mRNA.
(2)We also identified other chaperons, HSP27, by analysis of UV-induced protease. The activity of removing 6-4 photo products after UV irradiation was decreased when expression of HSP27 was suppressed. We further identified that GRP78 is also involved in the repair mechanism for the UV-induced damage. Thus, the modulation of cell mutability by chaperons seems to be mediated though protease signaling.
(3)One of ubiquitin-like proteins, SUMO-3, was identified as a candidate gene for abnormal DNA synthesis activity after X-ray irradiation. It is known that the function of SUMO-3 is regulated by specific proteases. The activity of DNA synthesis after X-ray irradiation was increased when expression of SUMO-3 was decreased. We expressed GFP-SUMO-3 fusion protein and observed a marked concentration of green fluorescence in the nuclear after X-ray irradiation.
Application of a new method to evaluate oxidative stress in human serum. A test to monitor the oxidative stress by evaluating serum hydroperoxide was carried out. Serum hydrpperoxide of some patients and heavy-smokers showed higher levels than healthy volunteers.
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