| Full text | |
| Author(s): |
Guimaraes, Fabiana de Salvi
;
Almeida Monteiro de Moraes, Wilson Max
;
Marchesi Bozi, Luis Henrique
;
Souza, Pamela R.
;
Antonio, Ednei Luiz
;
Bocalini, Danilo Sales
;
Ferreira Tucci, Paulo Jose
;
Ribeiro, Daniel Araki
;
Brum, Patricia Chakur
;
Medeiros, Alessandra
Total Authors: 10
|
| Document type: | Journal article |
| Source: | Molecular and Cellular Biochemistry; v. 424, n. 1-2, p. 87-98, JAN 2017. |
| Web of Science Citations: | 5 |
| Abstract | |
Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (similar to 400 g) were treated with dexamethasone (35 A mu g/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na+/Ca2+ exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation. (AU) | |
| FAPESP's process: | 11/04699-3 - Effect of glucocorticoids on function and cardiac morphology in rats |
| Grantee: | Fabiana de Salvi Guimarães |
| Support Opportunities: | Scholarships in Brazil - Master |