Tropisetron inhibits high glucose-induced calcineurin/NFAT hypertrophic pathway in H9c2 myocardial cells.

Published on Apr 1, 2016in Journal of Pharmacy and Pharmacology2.39
· DOI :10.1111/jphp.12522
Firouzeh Asadi3
Estimated H-index: 3
(IUMS: Iran University of Medical Sciences),
Ali Razmi7
Estimated H-index: 7
+ 1 AuthorsMassoumeh Shafiei11
Estimated H-index: 11
(IUMS: Iran University of Medical Sciences)
Objectives 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. Key findings Exposure to HG resulted in enhanced cell size, protein content and atrial natriuretic peptide (ANP) protein expression. HG significantly increased Ca2+ 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 Ca2+ was not affected. Conclusion 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.
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