Regulation mechanisms of aquaporin in the brain and its functions in the brain edema

水通道蛋白在脑内的调节机制及其在脑水肿中的作用

• 批准号: 15591652
• 负责人: KATSUYA Hirotada
• 金额: $ 2.24万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591652/
• 关键词: Brain edema; Aquaporin; Central nervous system; Astrocytes; 蛋白結合蛋白; 培養細胞

Aquaporins (AQPs) are water channel proteins, which increase water permeability via the plasma membrane and thus provide a route for rapid fluid movement. In the brain, AQP4 is abundantly expressed, and is highly concentrated in astrocyte membranes that are in direct contact with capillaries and pia. AQP4 is considered a major pathway for massive water shift across the plasma membrane under various conditions and is involved in brain edema formation. However, little is known concerning the mechanisms by which AQP4 expression is regulated in the brain. We investigated molecules, which interact with AQP4 and discovered RIL as a binding protein. Actually, it is confirmed that RIL directly interacted with AQP4 by in vitro binding assay, pull down assay, co-immunoprecipitation, and immunohistochemical staining. We are preparing a vector for a RIL null mouse, which reveals the regulation mechanisms of AQP4 by RIL. It is possible that RIL is a target molecule for a new therapeutic method of brain edema.

水通道蛋白（AQP）是一种水通道蛋白，它通过质膜增加水的渗透性，从而为液体的快速运动提供了途径。在大脑中，AQP4大量表达，并且高度集中在与毛细血管和软脑膜直接接触的星形胶质细胞膜中。AQP4被认为是在各种条件下大量水转移穿过质膜的主要途径，并参与脑水肿形成。然而，关于AQP4在脑中表达的调节机制知之甚少。我们研究了与AQP4相互作用的分子，并发现RIL是一种结合蛋白。实际上，通过体外结合试验、下拉试验、免疫共沉淀和免疫组织化学染色证实RIL与AQP4直接相互作用。我们正在制备RIL基因敲除小鼠的载体，以揭示RIL对AQP4的调控机制。RIL有可能成为脑水肿治疗新方法的靶分子。

项目成果

Arima H: "Hyperosmotic mannitol stimulates expression of aquaporin 4 and 9 through a p38 mitogen activated kinase-dependent pathway in rat astrocytes."J.Biol.Chem.. 278. 44525-44534 (2003)

Arima H：“高渗甘露醇通过大鼠星形胶质细胞中的 p38 丝裂原激活激酶依赖性途径刺激水通道蛋白 4 和 9 的表达。”J.Biol.Chem.. 278. 44525-44534 (2003)

Interleukin-1β induces the expression of aquaporin-4 through a NF-κB pathway in rat astrocytes

Interleukin-1β 通过 NF-κB 通路诱导大鼠星形胶质细胞中水通道蛋白 4 的表达

• 发表时间: 2006
• 期刊: J Neurochem (印刷中)
• 作者: Fumihiko Yasuma;Jun-ichiro Hayano;Ito H
• 通讯作者: Ito H

Fujita Y: "Effect of Mild Hypothermia on the Expression of Aquaporin Family in Cultured Rat Astrocytes under Hypoxic Condition."Neurosci.Res.. 47. 437-444 (2003)

Fujita Y：“轻度低温对缺氧条件下培养的大鼠星形胶质细胞中水通道蛋白家族表达的影响。”Neurosci.Res.. 47. 437-444 (2003)

A case of complex regional pain syndrome type II after transradial coronary intervention.

• DOI: 10.1007/s00540-004-0266-0
• 发表时间: 2004-01-01
• 期刊: Journal of anesthesia
• 影响因子: 2.8
• 作者: Sasano, Nobuko;Tsuda, Takako;Katsuya, Hirotada
• 通讯作者: Katsuya, Hirotada

Effect of mild hypothermia on the expression of aquaporin family in cultured rat astrocytes under hypoxic condition

• DOI: 10.1016/j.neures.2003.08.006
• 发表时间: 2003-12-01
• 期刊: NEUROSCIENCE RESEARCH
• 影响因子: 2.9
• 作者: Fujita, Y;Yamamoto, N;Asai, K
• 通讯作者: Asai, K