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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 Razmi6
Estimated H-index: 6
+ 1 AuthorsMassoumeh Shafiei11
Estimated H-index: 11
(IUMS: Iran University of Medical Sciences)
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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 (51)
  • Citations (6)
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References51
Newest
#1Andrea C. Tricco (U of T: University of Toronto)H-Index: 35
#2Charlene Soobiah (U of T: University of Toronto)H-Index: 16
Last.Heather MacDonald (St. Michael's Hospital)H-Index: 17
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#1Anita Barzegar-Fallah (IUMS: Iran University of Medical Sciences)H-Index: 3
#2Houman Alimoradi (University of Otago)H-Index: 5
Last.Massoumeh Shafiei (IUMS: Iran University of Medical Sciences)H-Index: 11
view all 6 authors...
#1Naser Abbasi (IUMS: Iran University of Medical Sciences)H-Index: 6
#2Maziar Mohammad Akhavan (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 6
Last.Massoumeh Shafiei (IUMS: Iran University of Medical Sciences)H-Index: 11
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#1Meng Du (HUST: Huazhong University of Science and Technology)H-Index: 6
#2Kun Huang (HUST: Huazhong University of Science and Technology)H-Index: 7
Last.Dan Huang (HUST: Huazhong University of Science and Technology)H-Index: 10
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#1Houman AlimoradiH-Index: 5
#2Anita Barzegar-Fallah (Tehran University of Medical Sciences)H-Index: 2
Last.Ahmad Reza Dehpour (Tehran University of Medical Sciences)H-Index: 38
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#1Rong Huo (Ministry of Education)H-Index: 1
#2Chang Chen (Ministry of Education)H-Index: 1
Last.Deli Dong (Ministry of Education)H-Index: 1
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Cited By6
Newest
#1Kai-Chun Cheng (Kadai: Kagoshima University)H-Index: 11
#2Yingxiao Li (Kadai: Kagoshima University)H-Index: 8
Last.Cheng-Chia Tsai (Mackay Memorial Hospital)
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#1Reza Rahimian (Laval University)H-Index: 18
#2Mohammad Reza Zirak (MUMS: Mashhad University of Medical Sciences)H-Index: 3
Last.Kazem Mousavizadeh (IUMS: Iran University of Medical Sciences)H-Index: 13
view all 9 authors...
View next paper[Effects of hydrogen sulfide (H2S) on cardiac hypertrophy and miRNA-133a-mediated Ca2+/calcineurin/NFATc4 signal pathway in rats].