Molecular chaperon HSP regulates apoptosis signaling
| Project/Area Number |
16591863
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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 |
Functional basic dentistry
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| Research Institution | Iwate Medical University |
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Principal Investigator |
KYAKUMOTO Seiko Iwate Med.Univ., Sch.Dent., Dept.Biochem., Assistant Professor, 歯学部, 講師 (90118274)
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| Co-Investigator(Kenkyū-buntansha) |
KAMO Masaharu Iwate Med.Univ., Sch.Dent., Dept.Biochem., Associate Professor, 歯学部, 助教授 (40214564)
CHOSA Naoyuki Iwate Med.Univ., Sch.Dent., Dept.Biochem., Research Associate, 歯学部, 助手 (80326694)
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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 |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | HSP90 / geldanamycin / Fas / apootosis / FLIP / caspase / 熱ショックタンパク質 / HSP |
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| Research Abstract |
In this study, the involvement of heat shock protein 90 in the anti-Fas antibody (CH-11)-induced apoptosis in HSG cells was investigated using geldanamycin (GDM), the specific inhibitor of HSP90. GDM itself caused the apoptosis in HSG cells, and moreover, it enhanced CH-11-induced apoptosis. RT-PCR and Westernblotting revealed that the expression of HSP90 was up-regulated by GDM, suggesting that the immediate complementation of HSP90 occurs after the functional inhibition of HSP90 by GDM. Further, the transfection of HSP90 protein into HSG cells significantly inhibited the enhancement of CH-11-induced apoptosis by GDM. Immunoprecipitation-Westernblotting analysis revealed FLIP, Caspase 8 and RIP as target proteins of HSP90. FLIP mRNA level was significantly decreased by GDM treatment. From these results, it was revealed that HSP90 negatively regulates Fas-induced apoptosis through its chaperoning effect on FLIP, the dominant-negative Caspase 8. Furthermore, we examined the transcription activation from the heat shock element-harboring luciferase reporter gene that was transfected into HSG cells. Treatment of the transfected cells with GDM, as well as heat shock treatment, increased the luciferase activity as compared with the untreated cells. This result suggested that GDM increases the expression of HSP90 through the dissociation of heat shock factor from HSPs and its following activation, translocation into nuclei, and then transcription activation of HSP90 gene.
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] DNA microarray analyses of gene expression in human mesenchymal stem cells cultured in osteogenic differentiation medium for 14 days.2005
Author(s)
Taira, M., Chosa, N., Sasaki, K., Saitoh, S., Nezu, T., Sato, N., Araki, Y.
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Journal Title
J.Oral Tissue Engin. 3(1)
Pages: 25-53
NAID
Description
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[Journal Article] A spatzle-processing enzyme required for Toll signaling activation in Drosophila innate immunity.2005
Author(s)
Jang, JR., Chosa, N., Kim, SH., Nam, HJ., Lemaitre, B., Ochiai, M., Kambris, Z., Brun, S., Hashimoto, C., Ashida, M., Brey, PT., Lee, WJ.
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Journal Title
Developmental Cell 10(1)
Pages: 45-55
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[Journal Article] Effects of the medium type, serum amount and dexamethasone induction on the cell proliferation and alkaline phosphatase activity of twice-passaged SD rats' bone marrow stromal cells.2004
Author(s)
Taira, M., Chosa, N, Sasaki, K., Saitoh, S., Sato, N., Takahashi, J., Araki, Y.
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Journal Title
J.Oral Tissue Engin. 1(1)
Pages: 59-68
NAID
Description
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