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Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation.
de Salvi Guimarães, Fabiana; de Moraes, Wilson Max Almeida Monteiro; Bozi, Luis Henrique Marchesi; Souza, Pâmela R; Antonio, Ednei Luiz; Bocalini, Danilo Sales; Tucci, Paulo José Ferreira; Ribeiro, Daniel Araki; Brum, Patricia Chakur; Medeiros, Alessandra.
Afiliação
  • de Salvi Guimarães F; Biosciences Department, Federal University of Sao Paulo, Silva Jardim, 136-Vl. Mathias, Santos, SP, 11015-020, Brazil.
  • de Moraes WM; Biosciences Department, Federal University of Sao Paulo, Silva Jardim, 136-Vl. Mathias, Santos, SP, 11015-020, Brazil.
  • Bozi LH; School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
  • Souza PR; Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
  • Antonio EL; Cardio-Physiology and Pathophysiology Laboratory, Federal University of Sao Paulo, São Paulo, Brazil.
  • Bocalini DS; Cardio-Physiology and Pathophysiology Laboratory, Federal University of Sao Paulo, São Paulo, Brazil.
  • Tucci PJ; Department of Post-Graduation in Physical Education, São Judas Tadeu University, São Paulo, Brazil.
  • Ribeiro DA; Cardio-Physiology and Pathophysiology Laboratory, Federal University of Sao Paulo, São Paulo, Brazil.
  • Brum PC; Biosciences Department, Federal University of Sao Paulo, Silva Jardim, 136-Vl. Mathias, Santos, SP, 11015-020, Brazil.
  • Medeiros A; School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
Mol Cell Biochem ; 424(1-2): 87-98, 2017 Jan.
Article em En | MEDLINE | ID: mdl-27761848
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 (~400 g) were treated with dexamethasone (35 µg/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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dexametasona / Cardiomegalia / Calcineurina / Sinalização do Cálcio / Miócitos Cardíacos / Miocárdio Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Mol Cell Biochem Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dexametasona / Cardiomegalia / Calcineurina / Sinalização do Cálcio / Miócitos Cardíacos / Miocárdio Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Mol Cell Biochem Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda