Stress signaling pathways responsible for the cell survival and death following exposure to toxic metals
| Project/Area Number |
26460175
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KOMOIKE Yuta 東京女子医科大学, 医学部, 講師 (70386556)
FUJIKI Koto 東京女子医科大学, 医学部, 助教 (80632504)
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| Research Collaborator |
MIYAYAMA Takamitsu
IWATSUKI Mamiko
INAMURA Hisako
MATSUMURA Kenichi
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 毒性金属 / 細胞死 / 細胞生存 / シグナル伝達 / 小胞体ストレス / カドミウム / Notch1 / ストレス応答 |
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| Outline of Final Research Achievements |
The toxic metal, cadmium, induces the activation of Notch1 signaling in renal proximal tubular cells and the resultant expression of Snail, a repressor of E-cadherin expression, leads to cellular damage by decreasing cell-cell adhesion. Cadmium-induced activation of Notch1 signaling also plays a role in the proliferation and malignant progression of lung cancer cells. Endoplasmic reticulum (ER) stress inhibitor salubrinal can protect cells from the damage induced by a wide range of xenotoxicants including toxic metals. Caenorhabditis elegans and zebrafish are a useful model for the analysis of the toxic metal or neurotoxic chemical-induced ER stress responses. In addition, effects of other toxic chemicals, including fluoride, silver nanoparticle, and acrylamide, on the intracellular signaling pathways responsible for their cytotoxicity were revealed in this study.
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Report
(4 results)
Research Products
(23 results)
