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

Author(s)

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

• Document type: Journal article
• Source: Parasitology Research; v. 116, n. 1, p. 5-pg., 2017-01-01.

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. (AU)

• FAPESP's process: 09/17787-8 - High blood pressure, cardiac hypertrophy, heart failure and dystrophin-glycoprotein complex
• Grantee: Cibele Maria Prado Zinni
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 10/19216-5 - Hypertension, cardiac hypertrophy and cardiac failure and dystrophin glycoproteins
• Grantee: Cibele Maria Prado Zinni
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 10/18629-4 - The role of calcium, calpain, pro-inflammatory cytokines and hypoxia on dystrophin expression in cardiomyocytes subjected to different stimuli: an in vitro study
• Grantee: Lygia Maria Mouri Malvestio
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)