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Original Paper
Biochemistry and Molecular Biology | Planta Med 2005; 71: 525-529
DOI: 10.1055/s-2005-864153 |
© Georg Thieme Verlag KG Stuttgart · New York |
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Molecular Mechanism of the Inhibitory Effect of Trilinolein on Endothelin-1-Induced Hypertrophy of Cultured Neonatal Rat Cardiomyocytes |
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| Shi-Chung Chen1,2, Jun-Jack Cheng3, Ming-Hsiung Hsieh1, Yen-Ling Chu4, Pai-Feng Kao1, Tzu-Hurng Cheng1,4, Paul Chan1,4 |
1 Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan
2 Institute of Clinical Medicine, National Yang-Ming University Medical College, Taipei, Taiwan
3 Division of Cardiology, Shin-Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan
4 Clinical Research Center, Taipei Medical University, Taipei, Taiwan |
Abstract
Trilinolein, isolated from the traditional Chinese herb Sanchi (Panax notoginseng), has been shown to have myocardial protective effects via its antioxidant ability. However, the cellular and molecular mechanisms of the protective effect of trilinolein in the heart remain to be elucidated. Oxidative mechanisms have been implicated in neonatal cardiomyocyte hypertrophy. We therefore have examined whether trilinolein attenuates reactive oxygen species (ROS) production and thus ET-1-induced hypertrophy of cardiomyocytes. Cultured neonatal rat cardiomyocytes were stimulated with ET-1 (10 nM), [3H]leucine incorporation and the β-myosin heavy chain (β-MyHC) promoter activity were examined. Trilinolein (1 and 10 μM) inhibited the ET-1-induced increase of [3H]-leucine incorporation in a concentration-dependent manner. Trilinolein (1 and 10 μM) also inhibited ET-1-induced β-MyHC promoter activity in cardiomyocytes. We further examined the effects of trilinolein on ET-1-induced intracellular ROS generation by measuring a redox-sensitive fluorescent dye, 2′,7′-dichlorofluorescin diacetate, fluorescence intensity. Trilinolein (1 and 10 μM) inhibited ET-1-increased intracellular ROS levels in a concentration-dependent manner. This increase of ROS by ET-1 (10 nM) or H2O2 (25 μM) was significantly inhibited by trilinolein (10 μM) and N-acetylcysteine (10 mM). Moreover, ET-1- or H2O2-induced β-MyHC promoter activity and protein synthesis were also inhibited by trilinolein (10 μM). These data indicate that trilinolein inhibits ET-1-induced β-MyHC promoter activity, and subsequent hypertrophy via its antioxidant ability in cardiomyocytes.
Key words
Trilinolein - endothelin-1 - cardiomyocyte hypertrophy - reactive oxygen species
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