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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)
Sources
Abstract
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.
  • References (48)
  • Citations (7)
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References48
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Abstract Due to their cardiac origin, H9c2 cells rank among the most popular cell lines in current cardiovascular research, yet molecular phenotype remains elusive. Hence, in this study we used proteomic approach to describe molecular phenotype of H9c2 cells in their undifferentiated (i.e., most frequently used) state, and its functional response to cardiotoxic drug doxorubicin. Of 1671 proteins identified by iTRAQ IEF/LC–MSMS analysis, only 12 proteins were characteristic for striated muscle ce...
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#2Houman Alimoradi (University of Otago)H-Index: 6
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Abstract Recent studies have shown that calcineurin plays a central role in hypertrophy and extracellular matrix (ECM) accumulation in glomeruli at the early stages of diabetic nephropathy. Tropisetron is an effective antiemetic drug which also can potently inhibit calcineurin. The aim of this study was to investigate whether tropisetron can prevent glomerular hypertrophy and ECM expansion in early diabetic nephropathy. Streptozotocin (STZ)-induced diabetic rats were treated with tropisetron and...
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#2Charlene Soobiah (U of T: University of Toronto)H-Index: 17
Last. Sharon E. Straus (U of T: University of Toronto)H-Index: 57
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#1Anita Barzegar-Fallah (IUMS: Iran University of Medical Sciences)H-Index: 4
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