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

Lygia M. Malvestio, Mara Rúbia N Celes, Linda A. Jelicks, Herbert B. Tanowitz, Cibele M. Prado

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalParasitology Research
DOIs
StateAccepted/In press - Oct 11 2016

Fingerprint

dystrophin
Dantrolene
Dystrophin
Trypanosoma cruzi
calpain
Calpain
mice
Serum
Cardiac Myocytes
Calcium
calcium
calcium channel blockers
myocarditis
Chagas disease
Chagas Disease
Cell Shape
muscular diseases
Myocarditis
Calcium Channel Blockers
heart diseases

Keywords

  • Calcium
  • Calpain
  • Cardiac myocytes
  • Chagas disease
  • Dantrolene
  • Dystrophin
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Parasitology
  • veterinary(all)
  • Insect Science
  • Infectious Diseases

Cite this

Malvestio, L. M., Celes, M. R. N., Jelicks, L. A., Tanowitz, H. B., & Prado, C. M. (Accepted/In press). Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice. Parasitology Research, 1-5. https://doi.org/10.1007/s00436-016-5281-1

Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice. / Malvestio, Lygia M.; Celes, Mara Rúbia N; Jelicks, Linda A.; Tanowitz, Herbert B.; Prado, Cibele M.

In: Parasitology Research, 11.10.2016, p. 1-5.

Research output: Contribution to journalArticle

Malvestio, Lygia M. ; Celes, Mara Rúbia N ; Jelicks, Linda A. ; Tanowitz, Herbert B. ; Prado, Cibele M. / Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice. In: Parasitology Research. 2016 ; pp. 1-5.
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