Dexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activation

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dc.citation.issue1/fev
dc.citation.volume424
dc.contributor.authorGuimaraes, Fabiana de Salvi [UNIFESP]
dc.contributor.authorMoraes, Wilson Max Almeida Monteiro de [UNIFESP]
dc.contributor.authorMarchesi Bozi, Luis Henrique
dc.contributor.authorSouza, Pamela R.
dc.contributor.authorAntonio, Ednei Luiz [UNIFESP]
dc.contributor.authorBocalini, Danilo Sales [UNIFESP]
dc.contributor.authorTucci, Paulo José Ferreira [UNIFESP]
dc.contributor.authorRibeiro, Daniel Araki [UNIFESP]
dc.contributor.authorBrum, Patricia Chakur
dc.contributor.authorMedeiros, Alessandra [UNIFESP]
dc.coverageDordrecht
dc.date.accessioned2020-07-31T12:46:58Z
dc.date.available2020-07-31T12:46:58Z
dc.date.issued2017
dc.description.abstractDexamethasone 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.en
dc.description.affiliationUniv Fed Sao Paulo, Biosci Dept, 136-V1 Mathias, BR-11015020 Santos, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Cardiophysiol & Pathophysiol Lab, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Judas Tadeu, Dept Postgraduat Phys Educ, Sao Paulo, Brazil
dc.description.affiliationUnifespBiosciences Department, Universidade Federal de São Paulo (UNIFESP), Santos, Brazil
dc.description.affiliationUnifespCardio-Physiology and Pathophysiology Laboratory, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 2011/04699-3
dc.format.extent87-98
dc.identifierhttp://dx.doi.org/10.1007/s11010-016-2846-3
dc.identifier.citationMolecular And Cellular Biochemistry. Dordrecht, v. 424, n. 43497, p. 87-98, 2017.
dc.identifier.doi10.1007/s11010-016-2846-3
dc.identifier.issn0300-8177
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56488
dc.identifier.wosWOS:000392107800008
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofMolecular And Cellular Biochemistry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectGlucocorticoidsen
dc.subjectCardiac dysfunctionen
dc.subjectCardiac hypertrophyen
dc.subjectCalcium homeostasisen
dc.titleDexamethasone-induced cardiac deterioration is associated with both calcium handling abnormalities and calcineurin signaling pathway activationen
dc.typeinfo:eu-repo/semantics/article
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