CaMKIIdelta overexpression in hypertrophy and heart failure: cellular consequences for excitation-contraction coupling
Braz. j. med. biol. res
; 38(9): 1293-1302, Sept. 2005. ilus, graf
Artigo
em Inglês
| LILACS
| ID: lil-408370
Biblioteca responsável:
BR1.1
ABSTRACT
Ca/calmodulin-dependent protein kinase IIdelta (CaMKIIdelta) is the predominant isoform in the heart. During excitation-contraction coupling (ECC) CaMKII phosphorylates several Ca-handling proteins including ryanodine receptors (RyR), phospholamban, and L-type Ca channels. CaMKII expression and activity have been shown to correlate positively with impaired ejection fraction in the myocardium of patients with heart failure and CaMKII has been proposed to be a possible compensatory mechanism to keep hearts from complete failure. However, in addition to these acute effects on ECC, CaMKII was shown to be involved in hypertrophic signaling, termed excitation-transcription coupling (ETC). Thus, animal models have shown that overexpression of nuclear isoform CaMKIIdeltaB can induce myocyte hypertrophy. Recent study from our laboratory has suggested that transgenic overexpression of the cytosolic isoform CaMKIIdeltaC in mice causes severe heart failure with altered intracellular Ca handling and protein expression leading to reduced sarcoplasmic reticulum (SR) Ca content. Interestingly, the frequency of diastolic spontaneous SR Ca release events (or opening of RyR) was greatly enhanced, demonstrating increased diastolic SR Ca leak. This was attributed to increased CaMKII-dependent RyR phosphorylation, resulting in increased and prolonged openings of RyR since Ca spark frequency could be reduced back to normal levels by CaMKII inhibition. This review focuses on acute and chronic effects of CaMKII in ECC and ETC. In summary, CaMKII overexpression can lead to heart failure and CaMKII-dependent RyR hyperphosphorylation seems to be a novel and important mechanism in ECC due to SR Ca leak which may be important in the pathogenesis of heart failure.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Base de dados:
LILACS
Assunto principal:
Cardiomegalia
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
Insuficiência Cardíaca
/
Contração Miocárdica
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2005
Tipo de documento:
Artigo
/
Congresso e conferência
/
Documento de projeto
País de afiliação:
Alemanha
Instituição/País de afiliação:
Georg-August-Universität Göttingen/DE