title: Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice.
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.
authors.affiliation: School of Medicine, IMED, Passo Fundo, RS, Brazil.|Laboratory of Cellular and Molecular Cardiology, Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Lygia M
authors.initials: LM
authors.lastname: Malvestio
authors.affiliation: Institute of Tropical Pathology and Public Health, Federal University of Goiás, Jataí, GO, Brazil.|Laboratory of Cellular and Molecular Cardiology, Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Mara Rúbia N
authors.initials: MR
authors.lastname: Celes
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Jelicks
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA. cibeleprado@usp.br.|Laboratory of Cellular and Molecular Cardiology, Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. cibeleprado@usp.br.
authors.forename: Cibele M
authors.initials: CM
authors.lastname: Prado
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D014355:Chagas Disease / Q000097:blood* / Q000473:pathology; D003620:Dantrolene / Q000494:pharmacology*; D016189:Dystrophin / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D051379:Mice; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D032383:Myocytes, Cardiac; D044967:Serum; D014349:Trypanosoma cruzi
chemical_list: D016189:Dystrophin; D009125:Muscle Relaxants, Central; D003620:Dantrolene
keywords: Calcium; Calpain; Cardiac myocytes; Chagas disease; Dantrolene; Dystrophin; Trypanosoma cruzi