Clarification of molecular mechanisms of endothelium-derived hyperpolarizing factor
阐明内皮源性超极化因子的分子机制
基本信息
- 批准号:16500266
- 负责人:
- 金额:$ 2.05万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2004
- 资助国家:日本
- 起止时间:2004 至 2005
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The purpose of this study was to clarify the molecular mechanisms of endothelium-derived hyperpolarizing factor (EDHF)-mediated arterial relaxation and membrane hyperpolarization in the rat mesenteric arteries. We tried to identify the ion channels, gap junctional channels and trp channels involved in the EDHF action. RT-PCR experiment showed that mRNA of small-conductance Ca^<2+>-activated K^+ (SK)3, intermediate-conductance Ca^<2+>-activated K^+(IK), large-conductance Ca^<2+>-activated K^+ (BK) channels and connexin-37, -40, -43, -45 but not SK1 and SK2 were exist in the rat mesenteric artery. cDNA of these ion channels and connexins were cloned by RT-PCR and cDNA library screening. New gene (SK3-b) similar to SK3 channel was cloned. The poly glutamine position of SK3 was substituted to poly serine in SK3-b. Functional analysis using patch clamp techniques showed that the SK3-b channel has almost the same ion channel functions such as voltage dependency and toxin sensitivity. However the Ca^<2+> sensitivity of the channel was less sensitive compared with that of the SK3. Immunohistochemical analysis showed that the SK3 channel was expressed in the endothelium. The CX37 and 43 were expressed in both the endothelial and smooth muscle cells, however CX40 was expressed in only the endothelial cells. To clarify the functional role of these genes in the native artery, adenoviruses expressing these genes were constructed. Adenovirus-mediated expression of SK3 or CX43 to the cultured rat mesenteric artery enhanced EDHF action slightly. Ovariectomy reduced the EDHF action in accordance with the reduced expression of CX40 and CX43
本研究旨在阐明内皮衍生超极化因子(EDHF)介导的大鼠肠系膜动脉松弛和膜超极化的分子机制。我们试图确定参与EDHF作用的离子通道、缝隙连接通道和色氨酸通道。RT-PCR结果显示,大鼠肠系膜动脉存在小电导钙激活钾通道、中导钙激活钾通道、大电导钙激活钾通道和连接蛋白-37、-40、-43、-45通道,而不存在连接蛋白-1和连接蛋白-2。通过RT-PCR和文库筛选的方法,克隆了这些离子通道和连接蛋白的基因。克隆了与SK3通道相似的新基因(SK3-b)。SK3-b中SK3的聚谷氨酰胺位被取代为聚丝氨酸。利用膜片钳技术进行的功能分析表明,SK3-b通道具有几乎相同的离子通道功能,如电压依赖性和毒素敏感性。然而,与SK3相比,该通道对钙离子的敏感性较低。免疫组织化学分析显示,SK3通道在内皮细胞中有表达。CX37和CX43在血管内皮细胞和平滑肌细胞中均有表达,而CX40仅在内皮细胞中表达。为了阐明这些基因在动脉中的功能作用,构建了表达这些基因的腺病毒。腺病毒介导的SK3或Cx43对培养的大鼠肠系膜动脉的EDHF作用略有增强。卵巢切除与CX40和Cx43表达减少有关的EDHF作用
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Reciprocal changes in endothelium-derived hyperpolarizing factor and nitric oxide-system in the mesenteric artery of adult female rats following ovariectomy.
卵巢切除术后成年雌性大鼠肠系膜动脉内皮衍生超极化因子和一氧化氮系统的相互变化。
- DOI:
- 发表时间:2005
- 期刊:
- 影响因子:0
- 作者:Nawate S;et al.
- 通讯作者:et al.
CSN5/Jab1 inhibits cardiac L-type Ca^<2+> channel activity through protein-protein interations.
CSN5/Jab1通过蛋白质-蛋白质相互作用抑制心脏L-型Ca^2通道活性。
- DOI:
- 发表时间:2006
- 期刊:
- 影响因子:0
- 作者:Inui K;Wang X;Tamura Y et al.;Inui K et al.;原口裕次ほか;Y.Itabashi et al.;H.Sekine et al.;T.Shimizu et al.;H.Sekine et al.;Kazutoshi Kameda
- 通讯作者:Kazutoshi Kameda
CSN5/Jab1 inhibits cardiac L-type Ca2+ channel activity through protein-protein interactions
- DOI:10.1016/j.yjmcc.2006.01.007
- 发表时间:2006-04-01
- 期刊:
- 影响因子:5
- 作者:Kameda, K;Fukao, M;Tohse, N
- 通讯作者:Tohse, N
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FUKAO Mitsuhiro其他文献
FUKAO Mitsuhiro的其他文献
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{{ truncateString('FUKAO Mitsuhiro', 18)}}的其他基金
Cloning and functional analysis of the target ion channel of endothelium-derived hyperpolarizing factor
内皮源性超极化因子靶离子通道的克隆及功能分析
- 批准号:
12670076 - 财政年份:2000
- 资助金额:
$ 2.05万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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上皮钠离子通道(ENaC)在血管内皮的功能和作用
- 批准号:81170236
- 批准年份:2011
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- 项目类别:面上项目
体外构建角膜内皮细胞膜片行后弹力层内皮移植后的功能评价
- 批准号:31140025
- 批准年份:2011
- 资助金额:10.0 万元
- 项目类别:专项基金项目
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