| Project/Area Number |
08672606
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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 |
応用薬理学・医療系薬学
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUDA Toshio Osaka Univeristy, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (00107103)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Na^+-Ca^<2+> exchanger / antiporter / cell death / reperfusion injury / astrocyte / calcineurin / FK506 / FK506 / 一酸化窒素 |
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| Research Abstract |
This studies were aimed to clarify the pathophysiological roles of the Na^+-Ca^<2+> exchanger (NCX) in glial cells. The following results were obtained. 1) Receptor operated Ca^<2+> signal is regulated by NCX in the forward mode. 2) Ca^<2+> repletion after Ca^<2+> depletion causes an increase in intracellular Ca^<2+> concentration followed by cell death in cultured astrocytes. 3) This injury (Ca^<2+> paradox-like injury) is mediated by an activation of NCX in the reverse mode. 4) The Ca^<2+> paradox-like injury is attenuated by NCX inhibitors, heat shock protein and calcineurin inhibitors. 5) Heat shock protein and calcineurin inhibitors do not affect the change in intracellular Ca^<2+> induced by Ca^<2+> paradox. 6) Novel compounds inhibit NCX activity in astrocytes at nM level. 7) Hydrogen peroxide is involved in the Ca^<2+> paradox-like injury. 8) mRNA levels of rat brain NCX isoforms (NCX1, NCX2 and NCX3) are not changed by ischemia/reperfusion. 9) Competitive PCR analysis shows that main isoform of the NCX differs between neurons and astrocytes, and they have the different sensitivity to Na^+.
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