| Project/Area Number |
17590473
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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 |
Applied pharmacology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
KOBAYASHI Hideyuki University of Miyazaki, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40148953)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Akihiko University of Miyazaki, Faculty of Medicine, Professor, 医学部, 教授 (30131949)
YANAGITA Toshihiko University of Miyazaki, Faculty of Medicine, Associate, 医学部, 助手 (60295227)
YOKOO Hiroki University of Miyazaki, Faculty of Medicine, Associate, 医学部, 助手 (30332894)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | brain microvessel / aquaporin / endothelial cells / brain edema / raft / glucocorticoid / agrin / regulation of expression / アストロサイト / 網膜 |
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| Research Abstract |
We have studied the regulatory mechanisms of expression and localization of aquaporin (AQP) water channels in brain microvessels as molecules regulating water permeability between blood and brain, and have tried to their pathophysiological
The expression of AQP1 in cultured brain microvascular endothelial GP8 cells was increased by the treatment with dexamethasone, a glucocorticoid, by increasing transcription in a concentration-and time-dependent manner. AQP1 was concentrated in lipid microdomain rafts, suggesting that the interaction of AQP1 and lipid is important for intracellular transport of AQP1 and that the induction of AQP1 may be involved in the ameliorating effects of glucocorticoid in brain edema.
In addition, we have characterized agrin, an extracellular matrix protein, as a key molecule regulating the localization of AQP. The major isoform of agrin expressed in the brain microvessels was long N-terminal (LN) agrin, and its N-terminal contained a cluster of hydrophobic amino, a putative signal sequence for secretion. The N-terminal of LN agrin fused with green fluorescence protein was secreted into extracellular milieu. It is suggested that LN agrin expressed by the brain microvessels may regulate the localization of AQPs at the interface between brain microvessels and astrocytes.
To know role of AQP in the edema formation in the CNS, we have investigated the expression of AQP4 in the retina during endotoxin-induced uveitis in rats. The expression of AQP4 in the Muller cells facing the microvessels reduced slightly after endotoxin treatment, then returned to the control level. The expression of Kir4.1 potassium channel reduced to less than half by the endotoxin treatment, and remained at low level. The differential expression of AQP4 and Kir4.1 during endotoxin-induced uveitis implies a disturbance of water and potassium transport in the retina, which may contribute to the retinal edema during ocular inflammation.
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