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Title: Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation
Authors: Guimaraes, Fabiana de Salvi [UNIFESP]
Moraes, Wilson Max Almeida Monteiro de [UNIFESP]
Marchesi Bozi, Luis Henrique
Souza, Pamela R.
Antonio, Ednei Luiz [UNIFESP]
Bocalini, Danilo Sales [UNIFESP]
Tucci, Paulo José Ferreira [UNIFESP]
Ribeiro, Daniel Araki [UNIFESP]
Brum, Patricia Chakur
Medeiros, Alessandra [UNIFESP]
Keywords: Glucocorticoids
Cardiac dysfunction
Cardiac hypertrophy
Calcium homeostasis
Issue Date: 2017
Publisher: Springer
Citation: Molecular And Cellular Biochemistry. Dordrecht, v. 424, n. 43497, p. 87-98, 2017.
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.
ISSN: 0300-8177
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