Your browser doesn't support javascript.
loading
Oxidized CaMKII (Ca2+/Calmodulin-Dependent Protein Kinase II) Is Essential for Ventricular Arrhythmia in a Mouse Model of Duchenne Muscular Dystrophy.
Wang, Qiongling; Quick, Ann P; Cao, Shuyi; Reynolds, Julia; Chiang, David Y; Beavers, David; Li, Na; Wang, Guoliang; Rodney, George G; Anderson, Mark E; Wehrens, Xander H T.
Afiliação
  • Wang Q; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Quick AP; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Cao S; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Reynolds J; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Chiang DY; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Beavers D; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Li N; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Wang G; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Rodney GG; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Anderson ME; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
  • Wehrens XHT; Department of Molecular Physiology and Biophysics (Q.W., A.P.Q., S.C., J.R., D.Y.C., D.B., N.L., G.W., G.G.R., X.H.T.W.), Department of Medicine (Cardiology) (N.L., X.H.T.W.), Department of Pediatrics (Cardiology) (X.H.T.W.), and Center for Space Medicine (X.H.T.W.), Baylor College of Medicine, Hous
Circ Arrhythm Electrophysiol ; 11(4): e005682, 2018 04.
Article em En | MEDLINE | ID: mdl-29654126
ABSTRACT

BACKGROUND:

Duchenne muscular dystrophy patients are prone to ventricular arrhythmias, which may be caused by abnormal calcium (Ca2+) homeostasis and elevated reactive oxygen species. CaMKII (Ca2+/calmodulin-dependent protein kinase II) is vital for normal Ca2+ homeostasis, but excessive CaMKII activity contributes to abnormal Ca2+ homeostasis and arrhythmias in cardiomyocytes. Reactive oxygen species induce CaMKII to become autonomously active. We hypothesized that genetic inhibition of CaMKII oxidation (ox-CaMKII) in a mouse model of Duchenne muscular dystrophy can alleviate abnormal Ca2+ homeostasis, thus, preventing ventricular arrhythmia. The objective of this study was to test if selective loss of ox-CaMKII affects ventricular arrhythmias in the mdx mouse model of Duchenne muscular dystrophy. METHODS AND

RESULTS:

5-(6)-Chloromethyl-2,7-dichlorodihydrofluorescein diacetate staining revealed increased reactive oxygen species production in ventricular myocytes isolated from mdx mice, which coincides with elevated ventricular ox-CaMKII demonstrated by Western blotting. Genetic inhibition of ox-CaMKII by knockin replacement of the regulatory domain methionines with valines (MM-VV [CaMKII M281/282V]) prevented ventricular tachycardia in mdx mice. Confocal calcium imaging of ventricular myocytes isolated from mdxMM-VV mice revealed normalization of intracellular Ca2+ release events compared with cardiomyocytes from mdx mice. Abnormal action potentials assessed by optical mapping in mdx mice were also alleviated by genetic inhibition of ox-CaMKII. Knockout of the NADPH oxidase regulatory subunit p47 phox normalized elevated ox-CaMKII, repaired intracellular Ca2+ homeostasis, and rescued inducible ventricular arrhythmias in mdx mice.

CONCLUSIONS:

Inhibition of reactive oxygen species or ox-CaMKII protects against proarrhythmic intracellular Ca2+ handling and prevents ventricular arrhythmia in a mouse model of Duchenne muscular dystrophy.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Distrofia Muscular de Duchenne / Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina / Ventrículos do Coração Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Arritmias Cardíacas / Distrofia Muscular de Duchenne / Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina / Ventrículos do Coração Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2018 Tipo de documento: Article