| Project/Area Number |
15510043
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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 |
KITA Kazuko Chiba University, Graduated School of Medicine, Lecturer, 大学院・医学研究院, 講師 (80302545)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Toshikazu Chiba University, Graduated School of Medicine, Research associate, 大学院・医学研究院, 助手 (70270527)
唐田 清仲 千葉大学, 大学院・医学研究院, 助手 (90345017)
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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 |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | ER stress proteins / Bip / GRP78 / DNA damage / UV / human cells / sensitivity to cell death / DNA repair / molecular chaperone / 遺伝子変異誘導 |
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| Research Abstract |
In contrast to extensive studies on the roles of molecular chaperones in mammalian cell responses to DNA-damaging stresses, there are only a few reports about the roles of Bip/GRP78, an endoplasmic reticulum(ER) stress-induced molecular chaperone. To investigate whether Bip/GRP78 is involved in resistance to a DNA-damaging agent, UVC (principally 254 nm in wavelength), we established human cells with down-regulation of Bip/GRP78 by transaction of human RSa cells with antisense cDNA for Bip/GRP. We found that the transfected cells showed higher sensitivity to UVC-induced cell death than control cells transfected with the vector alone. In the antisense-cDNA transfected cells, the removal capacities of the two major types of UVC-damaged DNA (thymine dimers and (6-4) photoproducts) in vivo and DNA synthesis activity of whole cell extracts to repair UVC-irradiated plasmids in vitro were remarkably decreased compared with those in the control cells. Furthermore, the antisense-cDNA transfected cells also showed slightly higher sensitivity to cisplatin-induced cell death than the control cells. Cisplatin-induced DNA damage is primarily repaired by nucleotide excision repair, like UVC-induced DNA damage. The present results suggest that Bip/GRP78 plays a protective role against UVC-induced cell death possibly via nucleotide excision repair, at least in the human RSa cells tested.
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