title: Role of dystrophin in acute Trypanosoma cruzi infection.
abstract: Previous studies have demonstrated loss/reduction of dystrophin in cardiomyocytes in both acute and chronic stages of experimental Trypanosoma cruzi (T. cruzi) infection in mice. The mechanisms responsible for dystrophin disruption in the hearts of mice acutely infected with T. cruzi are not completely understood. The present in vivo and in vitro studies were undertaken to evaluate the role of inflammation in dystrophin disruption and its correlation with the high mortality rate during acute infection. C57BL/6 mice were infected with T. cruzi and killed 14, 20 and 26 days post infection (dpi). The intensity of inflammation, cardiac expression of dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability were evaluated. Cultured neonatal murine cardiomyocytes were incubated with serum, collected at the peak of cytokine production and free of parasites, from T. cruzi-infected mice and dystrophin, calpain-1, and NF-κB expression analyzed. Dystrophin disruption occurs at the peak of mortality and inflammation and is associated with increased expression of calpain-1, TNF-α, NF-κB, and increased sarcolemmal permeability in the heart of T. cruzi-infected mice at 20 dpi confirmed by in vitro studies. The peak of mortality occurred only when significant loss of dystrophin in the hearts of infected animals occurred, highlighting the correlation between inflammation, dystrophin loss and mortality.
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.
authors.forename: Lygia M
authors.initials: LM
authors.lastname: Malvestio
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil; Institute of Tropical Pathology and Public Health, Federal University of Goiás, GO, Brazil; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Mara R N
authors.initials: MR
authors.lastname: Celes
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Milanezi
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
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, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.
authors.forename: Marcos A
authors.initials: MA
authors.lastname: Rossi
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: cibeleprado@usp.br.
authors.forename: Cibele M
authors.initials: CM
authors.lastname: Prado
mesh_terms: D000208:Acute Disease; D000818:Animals; D002154:Calpain / Q000378:metabolism; D014355:Chagas Disease / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000276:immunology / Q000469:parasitology; D016328:NF-kappa B / Q000378:metabolism; D014349:Trypanosoma cruzi; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016189:Dystrophin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002154:Calpain
keywords: Calpain-1; Cardiomyocytes; Chagas disease; Dystrophin; Inflammation; Trypanosoma cruzi