Project/Area Number |
15380202
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Basic veterinary science/Basic zootechnical science
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Research Institution | Osaka Prefecture University |
Principal Investigator |
NAKAMURA Yoichi Osaka Prefecture University, Grad.School of Life and Environmental Sciences, Lab. of Integrative Physiology in Veterinary Science, Professor, 生命環境学研究科, 教授 (90180413)
|
Co-Investigator(Kenkyū-buntansha) |
MORIYAMA Mitsuaki Osaka Prefecture University, Grad.School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet.Science, Associate Professor, 生命環境学研究科, 助教授 (20275283)
FUJIMOTO Yuka Osaka Prefecture University, Grad.School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet.Science, Assistant Professor, 生命環境学研究科, 助手 (40405361)
KANNAN Yukiko Osaka Prefecture University, Grad.School of Agriculture and Biological Sciences, Lab. of Integrative Physiology in Vet.Science, Guest Investigator, 生命環境学研究科, 客員研究員 (80264810)
|
Project Period (FY) |
2003 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2005: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2003: ¥5,800,000 (Direct Cost: ¥5,800,000)
|
Keywords | Microglia / Astrocyte / EC-SOD / Amphotericin B / NOS / NO production / プリオン断片 / 一酸化窒素 / アミロイド断片 / 血清成分 / リポ蛋白 / βアミロイド / コレステロール |
Research Abstract |
It is unknown how affects Amphotericin B (AmB), reported to be a therapeutic drug against prion diseases, on microglial function. Cultured microglia prepared from rat new-born brain were stimulated to produce nitric oxide (NO) by prion peptide (106-126) (PrP), and also by AmB. The level of the NO production stimulated by AmB was enhanced by the presence of the PrP. These results suggest a certain interaction between AmB and PrP and the interaction modulates the microglial cell function. The elucidation of this interaction might be a key for the therapeutic mechanism of AmB against prion diseases. The physiological functions of prion protein is speculative; however, it is suggested that prion protein is involves in the, mechanism of Cu transport, which is an essential metal for superoxide dismutase (SOD), through cell membrane. We have established the method for the measurement of extracellular SOD (EC-SOD) activity in the living cells. The activities of EC-SOD of cultured astrocytes from rat embryo's brain decreased to a half after stimulation by lipopolysaccharide (LPS) for 24 hr, whereas the intracellular SODs (cytoplasmic and mitochondrial) increased. On the other hand, the activity of SOD in the culture medium increased by LPS dose-dependently. These results suggest that EC-SOD is released from cell surface into the medium. Astrocytes may play an important role for the regulation of brain parenchymal level of active oxygen species by changing localization of EC-SOD ; protecting surrounding neurons from oxidative stress.
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