The role of sodium calcium exchanger (NCX)on cardiac function.
钠钙交换器(NCX)对心脏功能的作用。
基本信息
- 批准号:12557062
- 负责人:
- 金额:$ 8万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2000
- 资助国家:日本
- 起止时间:2000 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The Na^+-Ca^<2+> exchanger (NCX) on the plasma membrane is thought to be the main calcium extrusion system from the cytosol to the extracellular space in many mammalian excitable cells including cardiac myocytes. Three mammalian isoforms of NCX (NCX1, NCX2 and NCX3) have been isolated and NCX1 is expressed at high levels in the heart. However, the pathophysiological role of NCX in the heart is still unclear because of lack of specific inhibitors of NCX. To determine the role of NCX in cardiac contraction and the development of cardiac hypertrophy, we imposed pressure overload on the heart of heterozygous NCX knockout (KO) mice by constricting transverse aorta and examined cardiac function and morphology at three weeks after operation. Although there was no difference in cardiac function between sham-operated KO mice and sham-operated wild type (WT) mice, KO mice showed higher left ventricular pressure, and better systolic function than WT mice in response to pressure overload. Northern blot analysis revealed that mRNA levels of sarcoplasmic reticulum Ca^<2+>-ATPase (SERCA2) were reduced by pressure overload in left ventricles of WT mice but not of KO mice. Hypertrophic changes with interstitial fibrosis were more prominent in KO mice than WT mice. These results suggest that reduction of NCX results in supernormalized cardiac function and causes marked cardiac hypertrophy in response to pressure overload.
质膜上的Na^+-Ca^<2+>交换器(NCX)被认为是许多哺乳动物可兴奋细胞(包括心肌细胞)从细胞质溶胶到细胞外空间的主要钙挤出系统。NCX的三种哺乳动物亚型(NCX1、NCX2和NCX3)已被分离出来,NCX1在心脏中高水平表达。然而,由于缺乏特异性的NCX抑制剂,NCX在心脏中的病理生理作用尚不清楚。为了确定NCX在心脏收缩和心肌肥厚发生中的作用,我们通过收缩NCX杂合敲除(KO)小鼠的横主动脉对心脏施加压力过载,并在术后3周检测心功能和形态学。虽然假手术KO小鼠和假手术野生型(WT)小鼠的心功能没有差异,但KO小鼠在压力过载时表现出高于WT小鼠的左心室压力和更好的收缩功能。Northern blot分析显示,压力过载导致WT小鼠左心室肌浆网Ca^<2+>- atp酶(SERCA2) mRNA水平降低,而KO小鼠则没有。与WT小鼠相比,KO小鼠间质纤维化的增生性变化更为明显。这些结果表明,NCX的减少会导致心功能异常,并在压力过载的情况下导致明显的心脏肥大。
项目成果
期刊论文数量(82)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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- 影响因子:0
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- 通讯作者:
Toko H.: "Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adulat Heart"J Biol Chem. 277. 24735-24743 (2002)
Toko H.:“Csx/Nkx2-5 是成年心脏中心肌细胞稳态和存活所必需的”J Biol Chem。
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- 影响因子:0
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Minamino T: "Role of telomore in endothelial dysfunction in atherosclerosis"Curr Opin Lipidol. 13. 537-543 (2002)
Minamino T:“端粒在动脉粥样硬化内皮功能障碍中的作用”Curr Opin Lipidol。
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- 影响因子:0
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Saito S.: "β-adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes."J Biol Chem. 275. 34528-33 (2000)
Saito S.:“β-肾上腺素能途径通过心肌细胞中的钙调磷酸酶激活诱导细胞凋亡。”J Biol Chem. 275. 34528-33 (2000)
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- 影响因子:0
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Takimoto E.: "Up-regulation of natriuretic peptides in the ventricle of Csx/Nkx2-5 transgenic mice"Biochem Biophys Res Comm. 270. 1074-1079 (2000)
Takimoto E.:“Csx/Nkx2-5 转基因小鼠心室中利钠肽的上调”Biochem Biophys Res Comm。
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Wnt信号在心肌细胞分化中的作用及其对心脏病治疗的意义
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21229010 - 财政年份:2009
- 资助金额:
$ 8万 - 项目类别:
Grant-in-Aid for Scientific Research (S)
Molecular mechanisms of cardiomyocyte differentiation and their therapeutic implications
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18209028 - 财政年份:2006
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$ 8万 - 项目类别:
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Molecular Mechanisms of Cardiomyocyte Differentiation
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15209025 - 财政年份:2003
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Molecular Mechanisms of Heat Failure and Its Novel Therapeutic Strategies
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12136101 - 财政年份:2000
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Establishment of cardiac myocyte cell line
心肌细胞系的建立
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06557042 - 财政年份:1994
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$ 8万 - 项目类别:
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Characterrization of cardiac specific specific homebox gene
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06454288 - 财政年份:1994
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$ 8万 - 项目类别:
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