Firouzeh Asadi1, Ali Razmi2, Ahmad Reza Dehpour3, Massoumeh Shafiei1. 1. Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. 2. Medicinal Plants Research Center, Institute of Medicinal Plants ACECR, Karaj, Iran. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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 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. 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.
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 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. 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.
Authors: Xianhui Liang; Bohan Chen; Pei Wang; Yan Ge; Deepak K Malhotra; Lance D Dworkin; Zhangsuo Liu; Rujun Gong Journal: Am J Transl Res Date: 2020-03-15 Impact factor: 4.060