Mechanical stretch induces endothelial nitric oxide synthase gene expression in neonatal rat cardiomyocytes

Tzu-Hurng Cheng, Jeremy J W Chen, Neng Lang Shih, Jia Wei Lin, Ju Chi Liu, Yen Ling Chen, Cheng Hsien Chen, Jin Jer Chen

研究成果: 雜誌貢獻文章

8 引文 (Scopus)

摘要

Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [ 3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.
原文英語
頁(從 - 到)559-566
頁數8
期刊Clinical and Experimental Pharmacology and Physiology
36
發行號5-6
DOIs
出版狀態已發佈 - 五月 2009

指紋

Nitric Oxide Synthase Type III
Cardiac Myocytes
Gene Expression
Phosphoglycerate Kinase
Genes
Nitric Oxide
Proteins
Nitric Oxide Donors
Cardiomegaly
Nitrites
Oligonucleotide Array Sequence Analysis
Cytoskeleton
Leucine
Northern Blotting
Hypertrophy
Cell Movement
Signal Transduction
Cell Cycle
Heart Failure
Complementary DNA

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

引用此文

Mechanical stretch induces endothelial nitric oxide synthase gene expression in neonatal rat cardiomyocytes. / Cheng, Tzu-Hurng; Chen, Jeremy J W; Shih, Neng Lang; Lin, Jia Wei; Liu, Ju Chi; Chen, Yen Ling; Chen, Cheng Hsien; Chen, Jin Jer.

於: Clinical and Experimental Pharmacology and Physiology, 卷 36, 編號 5-6, 05.2009, p. 559-566.

研究成果: 雜誌貢獻文章

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abstract = "Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [ 3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.",
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AU - Chen, Cheng Hsien

AU - Chen, Jin Jer

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AB - Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [ 3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.

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