Molecular mechanism of the inhibitory effect of trilinolein on endothelin-1-induced hypertrophy of cultured neonatal rat cardiomyocytes.
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 beta-myosin heavy chain (beta-MyHC) promoter activity were examined. Trilinolein (1 and 10 microM) inhibited the ET-1-induced increase of [3H]-leucine incorporation in a concentration-dependent manner. Trilinolein (1 and 10 microM) also inhibited ET-1-induced beta-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 microM) inhibited ET-1-increased intracellular ROS levels in a concentration-dependent manner. This increase of ROS by ET-1 (10 nM) or H2O2 (25 microM) was significantly inhibited by trilinolein (10 microM) and N-acetylcysteine (10 mM). Moreover, ET-1- or H2O2-induced beta-MyHC promoter activity and protein synthesis were also inhibited by trilinolein (10 microM). These data indicate that trilinolein inhibits ET-1-induced beta-MyHC promoter activity, and subsequent hypertrophy via its antioxidant ability in cardiomyocytes.
Chen
Shi-Chung
SC
Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
Cheng
Jun-Jack
JJ
Hsieh
Ming-Hsiung
MH
Chu
Yen-Ling
YL
Kao
Pai-Feng
PF
Cheng
Tzu-Hurng
TH
Chan
Paul
P
D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D016166:Free Radical Scavengers / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D005894:Panax; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D002316:Cardiotonic Agents; D019332:Endothelin-1; D016166:Free Radical Scavengers; D010936:Plant Extracts; D014280:Triglycerides; D018995:Myosin Heavy Chains; C009564:trilinolein