2004 Fiscal Year Final Research Report Summary
Role of ER stress sensor Bip/GRP78 in protection of genome stability from DNA damaging stresses
| 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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | ER stress proteins / Bip / GRP78 / DNA damage / UV / human cells / sensitivity to cell death / DNA repair / molecular chaperone |
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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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Research Products
(16 results)
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[Journal Article] Decreased cell survival and DNA repair capacity after UVC irradiation in association with down-regulation of GRP78/BiP in human Rsa cells.2005
Author(s)
Zhai, L., Kita, K., Wano, C., Wu, Y., Sugaya, S., Suzuki, N.
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Protective role of HSP27 against UVC-induced cell death in human cells.2004
Author(s)
Wano, C., Kita, K., Takahashi, S., Sugaya, S., Hino, M., Hosoya, H., Suzuki, K.
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Journal Title
Exp.Cell Res. 298
Pages: 584-592
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Involvement of human small fragment nuclease in the resistance of human cells to UVC-induced cell death.2004
Author(s)
Ito, S., Kita, K., Zhai, L., Wano, C., Suzuki, T., Yamamura, A., Suzuki, N.
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Journal Title
Photochem.Photobiol. 80
Pages: 281-285
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Induction of uPA release in human peripheral blood lymphocytes by [deamino-Cys1,D-Arg8]-vasopressin (dDAVP).2004
Author(s)
Yamaguchi, Y., Yamada, K., Suzuki, T., Wu Y-P., Kita K., Takahashi, S., Ichinose, M., Suzuki, N.
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Journal Title
Am.J.Phsiol Endocrinol Metab. 287
Pages: E970-E97
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Induction of apoptosis and ubiquitin hydrolase gene expression by human serum factors in the early phase of acute myocardial infarction.2003
Author(s)
Hasegawa, R., Kita, K., Hasegawa, R., Fusejima, K., Fukuzawa, S., Wano, C., Watanabe, S., Saisho, H., Masuda, Y., Nomura, F., Suzuki, N.
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Journal Title
J.Lab.Clin.Med. 141
Pages: 168-178
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress : involvement of E-64-sensitive proteases on suppression of UV mutagenicity.2003
Author(s)
Takahashi, S., Hasegawa, R., Kita, K., Zhang, H-C., Wano, C., Yamaguchi, Y., Sugaya, S., Nomura, J., Ichinose, M., Suzuki, N.
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Journal Title
Cell Biol.Int. 27
Pages: 53-60
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Involvement of LEU13 in interferon-induced refractoriness of human RSa cells to X-ray cell killing.2003
Author(s)
Kita, K., Sugaya, S., Zhai, L., Wu, Y., Wano, C., Chigira, S., Nomura, J., Takahashi, S., Ichinose, M., Suzuki, N.
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Journal Title
Radiat.Res. 160
Pages: 302-308
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Increased expression of the huntington interacting protein-1 gene, in cells from Hutchinson Gilford syndrome (Progeria) patients and aged donors.2003
Author(s)
Chigira, S., Sugita, K., Kita, K., Sugaya, S., Arase, Y., Ichinose, M., Shirasawa, H., Suzuki, N
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Journal Title
J.Gerontology : Biological Sciences 58A
Pages: 873-878
Description
「研究成果報告書概要(和文)」より
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