Autonomous and growth factor - Induced hypertrophy in cultured neonatal mouse cardiac myocytes: Comparison with rat

Academic Article

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 β-adrenergic receptor, and leukemia inhibitory factor induced hypertrophy by a 20% to 30% increase in [3H]phenylalanine-labeled protein content. T3 and NE also increased α-myosin heavy chain (MyHC) mRNA and reduced β-MyHC. In contrast, hypertrophic stimuli in rat myocytes, including α1-adrenergic agonists, endothelin-1, prostaglandin F(2α), interleukin 1β, 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 β-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 β-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

    Published In

    Digital Object Identifier (doi)

    Author List

  • Deng XF; Rokosh DG; Simpson PC
  • Start Page

  • 781
  • End Page

  • 788
  • Volume

  • 87
  • Issue

  • 9