title: Redox regulation of MAPK pathways and cardiac hypertrophy in adult rat cardiac myocyte.
abstract: OBJECTIVE
  We analyzed the regulatory function of reactive oxygen species (ROS) on the hypertrophic signaling in adult rat cardiac myocytes:
  
  
  BACKGROUND
  The ROS regulate mitogenic signal transduction in various cell types. In neonatal rat cardiac myocyte, antioxidants have been shown to inhibit cardiac hypertrophy, and ROS are suggested to modulate the hypertrophic signaling. However, the conclusion may not reflect the situation of mature heart, because of the different natures between neonatal and adult cardiac myocytes.
  
  
  METHODS
  Cultured adult rat cardiac myocytes were stimulated with endothelin-1 (ET-1) or phenylephrine (PE), and intracellular ROS levels, the activities of mitogen-activated protein kinases (MAPKs; ERK, p38, and JNK), and 3H-phenylalanine incorporation were examined. We also examined the effects of antioxidant pretreatment of myocytes on MAPK activities and cardiac hypertrophy to analyze the modulatory function of redox state on MAPK-mediated hypertrophic signaling.
  
  
  RESULTS
  The ROS levels in ET-1- or PE-stimulated myocytes were maximally increased at 5 min after stimulation. The origin of ROS appears to be from NADH/NADPH oxidase, because the increase in ROS was suppressed by pretreatment of myocytes with NADH/NADPH oxidase inhibitor diphenyleneiodonium. Extracellular signal-regulated kinase (ERK) activity was increased by the stimulation of ET-1 or PE. In contrast, p38 and c-Jun-N-terminal protein kinase (JNK) activities did not change after these stimulations. Antioxidant treatment of myocytes suppressed the increase in ROS and blocked ERK activation and the subsequent cardiac hypertrophy induced by these stimuli.
  
  
  CONCLUSIONS
  These data demonstrate that ROS mediate signal transduction of cardiac hypertrophy induced by ET-1 or PE in adult rat cardiac myocytes.
authors.affiliation: 4th Department of Internal Medicine, Shimane Medical University, Japan. tanakak@shimane-med.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: T
authors.initials: T
authors.lastname: Takabatake
mesh_terms: D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D010084:Oxidation-Reduction; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D019332:Endothelin-1; D017382:Reactive Oxygen Species; D010656:Phenylephrine; D020928:Mitogen-Activated Protein Kinases