The role of the small GTP binding protein, rho, in the vascular smooth muscle.

小 GTP 结合蛋白 rho 在血管平滑肌中的作用。

基本信息

  • 批准号:
    11838013
  • 负责人:
  • 金额:
    $ 2.69万
  • 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:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

The small G protein, rho, has been shown to inhibit myosin light chain phosphatase (MLCP) through the phosphorylation of this enzyme by rho kinase. It was thus obvious that MLCP may be the key protein for the rho-mediated signal transduction to induce modulation of calcium sensitivity of the vascular smooth muscle. MLCP is composed of three subunits, namely, catalytic subunit, small regulatory subunit and large regulatory subunit. We focused on the function of two regulatory subunits of MLCP on the smooth muscle contractile apparatus in the present research program. The major findings were as follows.1. The effects of the small regulatory subunit of myosin light chain phosphatase (MLCPsr) on the Ca^<2+>-induced contraction of smooth muscle were investigated in the Triton X-100-permeabilized porcine renal artery. The full-length recombinant chicken MLCPsr obtained by the bacterial expression system induced an additional contraction at a constant [Ca^<2+>] i and shifted the [Ca^<2+>] i-f … More orce relation curve to the left. A deletion mutant containing the N-terminal 78 amino acids of MLCPsr retained the full action, compared with the full-length MLCPsr, while the deletion of this region completely abolished its effect. The process of relaxation was also delayed by the fragment containing the N-terminal 78 amino acids. These results indicated that MLCPsr increases the Ca^<2+> sensitivity of the contractile apparatus while the N-terminal 78 amino acids are responsible for this effect in vascular smooth muscle.2. The effects of the NH2-terminal fragments of the large regulatory subunit of myosin light chain phosphatase (MLCPlr) on the Ca^<2+>-induced contraction of smooth muscle were investigated in the Triton X-100-permeabilized porcine renal artery. MLCPlr 1-374, MLCPlr 304-511 and MLCPlr 297-374 induced leftward shifts of the [Ca^<2+>] i-force relationship. Deletion of residues 304-374 from the most potent construct, MLCPlr 1-374, abolished the Ca^<2+>-sensitizing effect. M1301-374 slowed the rate of relaxation in Ca^<2+>-free medium. The levels of myosin light chain phosphorylation (22.4%) and force (34.5%) obtained with 300 nM Ca^<2+> were increased by 3 microMMLCPlr 1-374 to 35.7 and 92.2%, respectively.These results indicated that the NH2-terminal MLCPlr fragments containing residues 304-374 inhibited myosin phosphatase, increased myosin light chain phosphorylation and increased the Ca^<2+> sensitivity of the contractile apparatus in permeabilized porcine renal artery.3. We have isolated cDNAs for heart-specific small regulatory subunit of myosin light chain phosphatase (HS-MLCPsr) that were transcribed from a heart-specific promoter in intron 13 of the MYPT2 gene. Functional analysis in permeabilized rat cardiac myocytes and porcine renal artery revealed that HS-MLCPsr enhanced Ca^<2+>-induced contraction, and the main functional domain was mapped in the N-terminal half of HS-MLCPsr. In addition, HS-MLCPsr bound to C-terminal one-third of MYPT1, and the binding domain was also mapped in the N-terminal half of HS-MLCPsr. These results indicated that HS-MLCPsr plays a role in regulation of the cardiac muscle contraction via binding to MYPT1. Less
小G蛋白rho已被证明通过rho激酶磷酸化肌球蛋白轻链磷酸酶(MLCP)来抑制该酶。由此可见,MLCP可能是rho介导的信号转导诱导血管平滑肌钙敏感性调节的关键蛋白。MLCP由三个亚基组成,即催化亚基、小调控亚基和大调控亚基。本研究重点研究了MLCP的两个调控亚基在平滑肌收缩器中的作用。主要研究结果如下:研究了肌球蛋白轻链磷酸酶小调控亚基(MLCPsr)对Ca^<2+>-诱导的猪肾动脉平滑肌收缩的影响。通过细菌表达系统获得的全长重组鸡MLCPsr诱导了一个恒定的[Ca^<2+>] i的额外收缩,并使[Ca^<2+>] i-f向左移动。与全长MLCPsr相比,含有MLCPsr n端78个氨基酸的缺失突变体保留了全部作用,而该区域的缺失则完全取消了其作用。含有n端78个氨基酸的片段也延缓了弛豫过程。这些结果表明,MLCPsr增加了血管平滑肌中Ca^<2+>的敏感性,而n端78个氨基酸负责这种作用。研究了肌球蛋白轻链磷酸酶(MLCPlr)大调控亚基nh2末端片段对Ca^<2+>诱导的猪肾动脉平滑肌收缩的影响。MLCPlr 1-374、MLCPlr 304-511和MLCPlr 297-374诱导了[Ca^<2+>] i-力关系的左移。从最有效的构建体MLCPlr 1-374中删除残基304-374,取消了Ca^<2+>-敏化作用。M1301-374减慢了Ca^<2+>-free介质中的弛豫速率。300 nM Ca^<2+>时,肌球蛋白轻链磷酸化水平(22.4%)和力(34.5%)分别增加了3 microMMLCPlr 1-374至35.7%和92.2%。这些结果表明,nh2末端含有残基304-374的MLCPlr片段抑制肌球蛋白磷酸酶,增加肌球蛋白轻链磷酸化,增加了通透性猪肾动脉收缩器Ca^<2+>的敏感性。我们从MYPT2基因13内含子的心脏特异性启动子中分离出心肌蛋白轻链磷酸酶(HS-MLCPsr)小调控亚基的cdna。对通透化大鼠心肌细胞和猪肾动脉的功能分析表明,HS-MLCPsr增强了Ca^<2+>诱导的收缩,主要功能域定位在HS-MLCPsr的n端半部分。此外,HS-MLCPsr与MYPT1的c端1 / 3结合,结合结构域也被定位在HS-MLCPsr的n端1 / 2。这些结果表明HS-MLCPsr通过与MYPT1结合来调节心肌收缩。少

项目成果

期刊论文数量(78)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Zhou YB: "The exogenously added small subunit of smooth muscle myosin phosphatase increases the Ca^<2+> sensitivity of the contractileapparatus in the permeabilizedporcine renal artery."Biochem Biophys Res Commun. 254. 158-163 (1999)
Zhou YB:“外源添加的平滑肌肌球蛋白磷酸酶小亚基增加了透化猪肾动脉中收缩装置的Ca 2+ 敏感性。”Biochem Biophys Res Commun。
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    0
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Yasutsune T: "Vasorelaxation and inhibition of the voltage-operated Ca^<2+> channelsby FK506 in the porcine coronary artery."Br J Pharmacol. 126. 717-729 (1999)
Yasutsune T:“猪冠状动脉中FK506对电压操作的Ca 2+ 通道的血管舒张和抑制。”Br J Pharmacol。
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    0
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Shintani Y: "Enhanced contractile response to thrombin in the pregnant rat myometrium."Br J Pharmacol. 131. 1619-1628 (2000)
Shintani Y:“怀孕大鼠子宫肌层对凝血酶的收缩反应增强。”Br J Pharmacol。
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    0
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Toshima J: "Differential effects of progesterone and 17 β-estradiol on the Ca^<2+> entry induced by thapsigargin and endothelin-1 in in situ endothelial cells."Biochem Biophys Acta. 1499. 109-12 (2000)
Toshima J:“黄体酮和 17 β-雌二醇对毒胡萝卜素和内皮素-1 在原位内皮细胞中诱导的 Ca^2+ 进入的不同影响。”Biochem Biophys Acta。1499. 109-12 (2000)。
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    0
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Kuroiwa-Matsumoto M, Hirano K, Ahmed A, Kawasaki J, Nishimura J, Kanaide H: "Mechanisms of the thapsigargin-induced Ca^<2+> entry in in situ endothelial cells of the porcine aortic valve and the endothelium-dependen relaxation in the porcine coronary arte
Kuroiwa-Matsumoto M、Hirano K、Ahmed A、Kawasaki J、Nishimura J、Kanaide H:“毒胡萝卜素诱导的 Ca^<2> 进入猪主动脉瓣原位内皮细胞的机制以及猪主动脉瓣内皮依赖性松弛的机制”
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NISHIMURA Junji其他文献

he change of conditions surrounding distribution and function of matching
分布条件和匹配功能的变化
業態の展開をもたらす卸売取引の連動性-チップワンストップの事例に基づき-
批发交易的环环相扣导致了业态的扩展 - 以 Chip One Stop 为例 -
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    西村順二;NISHIMURA Junji;NISHIMURA Junji;西村順ニ;西村順ニ;西村順二;西村順二
  • 通讯作者:
    西村順二
規制緩和と中小企業の新しい発展分野 : 地方都市における小売業段階の規制緩和と卸売業
中小企业的放松管制和新的发展领域:零售阶段的放松管制和地方城市的批发贸易
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    西村順二;NISHIMURA Junji;NISHIMURA Junji;西村順ニ;西村順ニ;西村順二
  • 通讯作者:
    西村順二
60 history of Osaka commerce
大阪商业60史
流通を取り巻く環境の変化と卸売業者の果たすペぎ懸隔架橋-新たなる卸売業者としてのドロップシッピングの可能性-
分销环境的变化以及批发商扮演的桥梁 - Dropshipping作为新批发商的可能性 -

NISHIMURA Junji的其他文献

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{{ truncateString('NISHIMURA Junji', 18)}}的其他基金

The Study of Japanese Distribution System in terms of Histrical Analysis in Global Market
从全球市场历史分析的角度研究日本流通制度
  • 批准号:
    23530558
  • 财政年份:
    2011
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Study of New Industry Characteristics in Wholesaling as Supporting Industry
批发配套产业新特征研究
  • 批准号:
    20530397
  • 财政年份:
    2008
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Non-myeloablative allogeneic stem cell transplantation in patients with systemic sclerosis
系统性硬化症患者的非清髓性同种异体干细胞移植
  • 批准号:
    16590983
  • 财政年份:
    2004
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
identification of a factor affection hair cycle in VDR null mouse
鉴定影响 VDR 缺失小鼠毛发周期的因素
  • 批准号:
    14571066
  • 财政年份:
    2002
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Analysis of Business Model of Interlocking of Wholesale Trade
批发贸易连锁经营模式分析
  • 批准号:
    13630129
  • 财政年份:
    2001
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The assessment of the contractility of the proliferating vascular smooth muscle
增殖血管平滑肌收缩力的评估
  • 批准号:
    13832006
  • 财政年份:
    2001
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
MECHANISMS FOR THE ACTION OF VASOACTIVE SUBSTANCES AND GROWTH FACTORS.
血管活性物质和生长因子的作用机制。
  • 批准号:
    05837016
  • 财政年份:
    1993
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
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