title: Autonomous and growth factor-induced hypertrophy in cultured neonatal mouse cardiac myocytes. Comparison with rat.
abstract: Cultured neonatal rat cardiac myocytes have been used extensively to study cellular and molecular mechanisms of cardiac hypertrophy. However, there are only a few studies in cultured mouse myocytes despite the increasing use of genetically engineered mouse models of cardiac hypertrophy. Therefore, we characterized hypertrophic responses in low-density, serum-free cultures of neonatal mouse cardiac myocytes and compared them with rat myocytes. In mouse myocyte cultures, triiodothyronine (T3), norepinephrine (NE) through a beta-adrenergic receptor, and leukemia inhibitory factor induced hypertrophy by a 20% to 30% increase in [(3)H]phenylalanine-labeled protein content. T3 and NE also increased alpha-myosin heavy chain (MyHC) mRNA and reduced beta-MyHC. In contrast, hypertrophic stimuli in rat myocytes, including alpha(1)-adrenergic agonists, endothelin-1, prostaglandin F(2alpha), interleukin 1beta, and phorbol 12-myristate 13-acetate (PMA), had no effect on mouse myocyte protein content. In further contrast with the rat, none of these agents increased atrial natriuretic factor or beta-MyHC mRNAs. Acute PMA signaling was intact by extracellular signal-regulated kinase (ERK1/2) and immediate-early gene (fos/jun) activation. Remarkably, mouse but not rat myocytes had hypertrophy in the absence of added growth factors, with increases in cell area, protein content, and the mRNAs for atrial natriuretic factor and beta-MyHC. We conclude that mouse myocytes have a unique autonomous hypertrophy. On this background, T3, NE, and leukemia inhibitory factor activate hypertrophy with different mRNA phenotypes, but certain Gq- and protein kinase C-coupled agonists do not.
authors.affiliation: VA Medical Center and the Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, California, USA.
authors.forename: X F
authors.initials: XF
authors.lastname: Deng
authors.forename: D G
authors.initials: DG
authors.lastname: Rokosh
authors.forename: P C
authors.initials: PC
authors.lastname: Simpson
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D005333:Fetus; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006984:Hypertrophy; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008858:Microscopy, Phase-Contrast; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D009218:Myosins / Q000032:analysis; D009638:Norepinephrine / Q000494:pharmacology; D010641:Phenotype; D010649:Phenylalanine / Q000032:analysis; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D006131:Growth Inhibitors; D006133:Growth Substances; D007375:Interleukin-1; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011506:Proteins; D012333:RNA, Messenger; D014284:Triiodothyronine; D010649:Phenylalanine; D009320:Atrial Natriuretic Factor; D015237:Dinoprost; D018995:Myosin Heavy Chains; D009218:Myosins; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine