Molecure targets and intracellular signal transduction in "Inflammation hypothesis" as pathology of cerebellum damage by methylmercury
| Project/Area Number |
15K21405
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Environmental and hygienic pharmacy
Hygiene and public health
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
YOSHIDA Eiko 東京理科大学, 薬学部薬学科, 助教 (50735488)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 水俣病 / メチル水銀 / 小脳障害 / 炎症仮説 / マクロファージ / T-リンパ球 / 小脳病変 / 炎症性サイトカイン |
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| Outline of Final Research Achievements |
Methylmercury is an environmental pollutant that induces serious neurological damage in the brain of humans and animals. Methylmercury-induced damage is localized in the granule cell layers in the cerebellum, although the mechanisms have been unclear. In the present study, it was revealed that methyl mercury elevates the expression of TNF-a by activating ERK, p38 MAPK, and NF-κB in macrophage-like RAW264.7 cells. Additionally, the damage of rat cerebellum granule cells caused by TNF-a was comparable with vascular endothelial cells, a cell type highly sensitive to the cytokine. Methylmercury increased the synthesis of both perforin and granzyme B through activation of the PTP1B-EGFR-MAPK pathway in Jurkat E6.1 cells. The present results support the hypothesis that inflammatory cells such as macrophages and cytotoxicic T-lymphocytes are involved in the selective damage of the granule cell layers in the cerebellum of methylmercury-exposed humans and animals via the TNF-a cytotoxicity.
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Report
(4 results)
Research Products
(20 results)
