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Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice

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Abstract

Dystrophin, an important protein of the dystrophin-glycoprotein complex, has been implicated in the pathogenesis of experimental Chagas disease. It is important for the maintenance of cell shape and contraction force transmission. Dystrophin loss has been related to end-stage cardiac myopathies and proposed as a common route for myocardial dysfunction and progression to advanced heart failure. Evidence suggests that calpains, calcium-dependent proteases, digest dystrophin when the calcium concentration is compatible with their activation. The objective of this in vitro study was to test the hypothesis that dantrolene, a calcium channel blocker, improves structural changes induced by serum from Trypanosoma cruzi-infected mice. Cultured neonatal cardiac myocytes were incubated with serum from T. cruzi-infected mice and treated with dantrolene for 24 h. Immunofluorescence and immunoblotting were performed to evaluate dystrophin and calpain-1 protein expression. The levels of dystrophin decreased 13 % and calpain increased 17 % after incubation of cultured neonatal cardiac myocytes with serum from T. cruzi-infected mice. The treatment with dantrolene restored the dystrophin and calpain levels near control levels. Our results demonstrate that alterations in calcium homeostasis in cardiac myocytes are responsible, in part, for cardiac structural changes in experimentally induced T. cruzi myocarditis and that calpain inhibitors may be beneficial in Chagasic heart disease.

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Acknowledgments

This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 09/17787-8; 09/53544-2; 10/18629-4; 10/19216-5).

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Authors and Affiliations

  1. School of Medicine, IMED, Passo Fundo, RS, Brazil

    Lygia M. Malvestio

  2. Institute of Tropical Pathology and Public Health, Federal University of Goiás, Jataí, GO, Brazil

    Mara Rúbia N. Celes

  3. Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA

    Linda A. Jelicks

  4. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA

    Herbert B. Tanowitz & Cibele M. Prado

  5. Laboratory of Cellular and Molecular Cardiology, Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Lygia M. Malvestio, Mara Rúbia N. Celes & Cibele M. Prado

Authors
  1. Lygia M. Malvestio
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  2. Mara Rúbia N. Celes
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  3. Linda A. Jelicks
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  4. Herbert B. Tanowitz
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  5. Cibele M. Prado
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Corresponding author

Correspondence to Cibele M. Prado.

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All protocols were approved by the Committee on Animal Research of School of Medicine of Ribeirão Preto, University of São Paulo, Brazil (Protocol 183/2010).

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Malvestio, L.M., Celes, M.R.N., Jelicks, L.A. et al. Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice. Parasitol Res 116, 429–433 (2017). https://doi.org/10.1007/s00436-016-5281-1

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  • DOI: https://doi.org/10.1007/s00436-016-5281-1

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