| Project/Area Number |
10470512
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
WATANABE Yasuo Tokyo Medical University, School of Medicine Associate Professor, 医学部, 助教授 (70183720)
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| Co-Investigator(Kenkyū-buntansha) |
HONMA Toyohiko Tokyo Medical University, School of Medicine Assistant Professor, 医学部, 講師 (60229268)
WATANABE Seigo Tokyo Medical University, School of Medicine Associate Professor, 医学部, 助教授 (10210907)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥9,200,000 (Direct Cost: ¥9,200,000)
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| Keywords | cellular environment / glia cells / synthetic condroitin sulfate / extracellular matrix / neuronal cells / cellular protection / NOx / 脳保護作用 / 細胞間環境 / 合成コンドロイチン硫酸化合物 / 細胞外マトリックス / 神経細胞 / 細胞保獲作用 / Calceine-am / 神経保護作用 / 新規コンドロイテン硫酸化合物 / LPS / グルタミン酸 / アポトーシス / 細胞間情報連絡系 / 細胞環境系 / 脳障害発現 / 神経保護 / 新規コンドロイチン硫酸化合物 / 細胞接着障害 |
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| Research Abstract |
In order to evaluate the functional role of glia cells in case of the brain functional diseases, the fluctuations of extracellular cytokines and nitric oxide produced from glia cell were examined under acidosis and endotoxin (LPS) treatment. A time-dependent and significant production of H_2O_2 was detected in the intracellular fluid of astrocyte-rich cultured cells under acidosis, although less production appeared in the neuron-rich cells. Additionally, microglia was detected in both cultured cells in the acidotic condition by the microscopic examination. By the treatment of H_2O_2, only astrocyte-containing cultured cells produced the delayed but marked increase of cytosolic Ca^<2+> levels and the sustained increase of extracellular IL-8. Correspondingly the cell injuries induced by H_2O_2 were observed, although much severe damages were seen in the astrocyte-less containing cells than in the astrocyte-rich cells. The cell damages and IL-8 production induced by H_2O_2 were significantly blocked in the absence of extracellular Ca^<2+> and by cyclosporine A and trifluoperazine. In the astrocyte-rich culture, but not in the astrocyte-less culture, increases of Ca^<2+>- dependent IL-8, TNF α and NOx productions induced by LPS were detected. The production of IL-8 from astrocyte may have a role in regulating the process of cell injury.
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