title: Tropisetron inhibits high glucose-induced calcineurin/NFAT hypertrophic pathway in H9c2 myocardial cells.
abstract: OBJECTIVE
  Cardiomyocyte hypertrophy is an important structural feature of diabetic cardiomyopathy. Calcineurin/nuclear factor of activated T-cell (NFAT) pathway plays a central role in the pathogenesis of cardiac hypertrophy. The purpose of this study was to investigate the effects of tropisetron, a novel calcineurin inhibitor, on high glucose (HG)-induced cardiomyocyte hypertrophy and its underlying mechanism.
  
  
  METHODS
  H9c2 myocardial cells were treated with tropisetron or cyclosporine A 1 h before exposure to HG for 48 h.
  
  
  RESULTS
  Exposure to HG resulted in enhanced cell size, protein content and atrial natriuretic peptide (ANP) protein expression. HG significantly increased Ca(2+) level, calcineurin expression and nuclear translocation of NFATc4. Both tropisetron and cyclosporine A markedly prevented the hypertrophic characteristic features, calcineurin overexpression and nuclear localization of NFATc4 while intracellular Ca(2+) was not affected.
  
  
  CONCLUSIONS
  Our results showed that tropisetron may have protective effects against HG-induced cardiomyocyte hypertrophy. The mechanism responsible for this beneficial effect seems to be, at least in part, blockade of calcineurin/NFAT signalling pathway.
authors.affiliation: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Firouzeh
authors.initials: F
authors.lastname: Asadi
authors.affiliation: Medicinal Plants Research Center, Institute of Medicinal Plants ACECR, Karaj, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Razmi
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Massoumeh
authors.initials: M
authors.lastname: Shafiei
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D019610:Cytoprotection; D058065:Diabetic Cardiomyopathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005947:Glucose / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D000077526:Tropisetron
chemical_list: D065095:Calcineurin Inhibitors; D007211:Indoles; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; C477593:Nfatc4 protein, rat; D000077526:Tropisetron; D009320:Atrial Natriuretic Factor; D019703:Calcineurin; D005947:Glucose; D002118:Calcium
keywords: H9c2; calcineurin; cardiomyocyte hypertrophy; high glucose; tropisetron