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Regulatory mechanisms of expression and localization of aquaporin water channels in brain microvessels

脑微血管中水通道蛋白水通道表达和定位的调控机制

基本信息

批准号：
17590473
负责人：
KOBAYASHI Hideyuki
金额：
$ 2.3万
依托单位：
University of Miyazaki
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590473/
关键词：
brain microvessel aquaporin endothelial cells brain edema raft glucocorticoid agrin regulation of expression アストロサイト網膜

项目摘要

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 pathophysiologicalThe 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.

本研究以脑微血管水通道蛋白（AQP）为研究对象，探讨其在脑微血管中的表达和定位的调控机制，并从病理生理学角度探讨其作用机制。AQP 1主要集中在脂质微区筏中，提示AQP 1与脂质的相互作用对AQP 1的胞内转运具有重要作用，AQP 1的诱导可能参与糖皮质激素对脑水肿的改善作用。在脑微血管中表达的聚集蛋白的主要同种型是长N-末端（LN）聚集蛋白，其N-末端含有一簇疏水性氨基，这是一个推测的分泌信号序列。LN聚集蛋白的N端融合绿色荧光蛋白后分泌到细胞外环境。提示脑微血管表达的LN agrin可能调节AQP在脑微血管与星形胶质细胞界面的定位。为了了解AQP在中枢神经系统水肿形成中的作用，我们观察了内毒素诱导的葡萄膜炎大鼠视网膜AQP 4的表达。内毒素处理后，面对微血管的Muller细胞中AQP 4的表达略有下降，然后恢复到对照水平。Kir4.1钾通道的表达在内毒素处理后下降到一半以下，并维持在低水平。AQP 4和Kir4.1在内毒素诱导的葡萄膜炎中的差异表达暗示了视网膜中水和钾转运的障碍，这可能有助于眼部炎症期间视网膜水肿。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Enhancement of insulin-induced PI3K/Akt/GSK-3beta and ERK signaling by neuronal nicotinic receptor/PKC-alpha/ERK pathway : up-regulation of IRS-1/-2 mRNA and protein in adrenal adrenal chromaffin cells.

通过神经元烟碱受体/PKC-α/ERK 途径增强胰岛素诱导的 PI3K/Akt/GSK-3beta 和 ERK 信号传导：肾上腺嗜铬细胞中 IRS-1/-2 mRNA 和蛋白质的上调。

DOI：
发表时间：
2006
期刊：
J. Neurochem. 98
影响因子：
0
作者：
Hideo ANBO;Noriyuki KONDO;Sugano T. et al.
通讯作者：
Sugano T. et al.

RELAXANT EFFECT OF ADRENOMEDULLIN ON BOVINE ISOLATED IRIS SPHINCTER MUSCLE UNDER RESTING CONDITIONS

静息条件下肾上腺髓质素对牛离体虹膜括约肌的松弛作用

DOI：
发表时间：
2005
期刊：
Clinical and Experimental Pharmacology and Physiology (32)
影响因子：
0
作者：
Uchikawa Y;Okano M;Sawada A;Asada Y;Kobayashi H;Wada A;Nao-i N;Ohkura M;Tanaka N;Yamamoto R;Y Uchikawa
通讯作者：
Y Uchikawa

Constitutive activity of glycogen synthase kinase-3beta : Positive regulation of steady-state levels of insulin receptor substrates-1 and -2 in adrenal chromaffin cells.

糖原合酶激酶-3β的组成活性：肾上腺嗜铬细胞中胰岛素受体底物-1和-2稳态水平的正向调节。