title: Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes.
abstract: BACKGROUND
  Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine with a broad range of concentration-dependent effects. The recent observation that TNF-alpha is expressed by the cardiac myocyte after certain forms of stress suggests that TNF-alpha might contribute to the maintenance of normal tissue homeostasis after environmental injury. Accordingly, the purpose of this study was to examine the effects of TNF-alpha on protein synthesis in cultured adult cardiac myocytes.
  
  
  RESULTS
  Cultured adult feline cardiac myocytes were stimulated with 10 to 1000 U/mL TNF-alpha to examine the effects of this cytokine on the rate of protein synthesis and degradation. Stimulation with TNF-alpha led to an accelerated rate of general protein synthesis and a time-dependent decrease in protein degradation in adult cardiac myocytes. The specificity of these findings was demonstrated by studies in which the effects of TNF-alpha on protein synthesis were blocked by a neutralizing anti-TNF-alpha antibody as well as studies in which TNF-alpha-conditioned medium had no effect on protein synthesis in myocytes. In addition to the TNF-alpha-induced increase in the general protein synthesis, stimulation with TNF-alpha led to a 2.4-fold increase in net actin protein synthesis and a 3.3-fold increase in net myosin heavy chain synthesis. Finally, the effects of TNF-alpha on adult cardiac myocytes were shown to be dependent on cell-substrate interaction, suggesting that the cell signaling pathways used by TNF-alpha are dependent on a preserved interaction between cell integrins and the extracellular matrix.
  
  
  CONCLUSIONS
  The observation that TNF-alpha provokes a hypertrophic growth response in cardiac myocytes suggests that TNF-alpha may play an important role in myocardial homeostasis after environmental stress.
authors.affiliation: Department of Medicine, Veterans Administration Medical Center, Houston, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Yokoyama
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.forename: J L
authors.initials: JL
authors.lastname: Bednarczyk
authors.forename: B W
authors.initials: BW
authors.lastname: McIntyre
authors.forename: M
authors.initials: M
authors.lastname: Entman
authors.forename: D L
authors.initials: DL
authors.lastname: Mann
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000704:Analysis of Variance; D000818:Animals; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects*; D006984:Hypertrophy; D007700:Kinetics; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000199:Actins; D009124:Muscle Proteins; D014409:Tumor Necrosis Factor-alpha; D018995:Myosin Heavy Chains