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 language | English (US) |
|---|---|
| Pages (from-to) | 1-5 |
| Number of pages | 5 |
| Journal | Parasitology Research |
| DOIs | |
| State | Accepted/In press - Oct 11 2016 |
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Keywords
- Calcium
- Calpain
- Cardiac myocytes
- Chagas disease
- Dantrolene
- Dystrophin
- Trypanosoma cruzi
ASJC Scopus subject areas
- Parasitology
- veterinary(all)
- Insect Science
- Infectious Diseases
Cite this
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 journal › Article
}
TY - JOUR
T1 - Dantrolene improves in vitro structural changes induced by serum from Trypanosoma cruzi-infected mice
AU - Malvestio, Lygia M.
AU - Celes, Mara Rúbia N
AU - Jelicks, Linda A.
AU - Tanowitz, Herbert B.
AU - Prado, Cibele M.
PY - 2016/10/11
Y1 - 2016/10/11
N2 - 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.
AB - 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.
KW - Calcium
KW - Calpain
KW - Cardiac myocytes
KW - Chagas disease
KW - Dantrolene
KW - Dystrophin
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=84991060673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991060673&partnerID=8YFLogxK
U2 - 10.1007/s00436-016-5281-1
DO - 10.1007/s00436-016-5281-1
M3 - Article
C2 - 27730362
AN - SCOPUS:84991060673
SP - 1
EP - 5
JO - Parasitology Research
JF - Parasitology Research
SN - 0932-0113
ER -