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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

c-Jun is regulated by combination of enhanced expression and phosphorylation in acute-overloaded rat heart

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Autor(es):
Nadruz Júnior, Wilson [1] ; Kobarg, Claudia B. ; Kobarg, Jorg ; Franchini, Kleber G. [4]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas - Brasil
[4] Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas. Departamento de Clínica Médica - Brasil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 286, n. 2, p. H760-H767, Feb. 2004.
Área do conhecimento: Ciências da Saúde - Medicina
Assunto(s):Sistema cardiovascular   Miocárdio   Expressão gênica   Antracenos   Proteínas quinases
Resumo

The transient increase in the expression of transcription factors encoded by immediate-early genes has been considered to play a critical role in the coordination of early gene expression during the hypertrophic growth of cardiac myocytes. Here, we investigated the regulation of c-Jun and its upstream activators JNKs in the myocardium of rats subjected to acute pressure overload induced by transverse aortic constriction. Western blotting and immunohistochemistry analysis demonstrated that both JNK1 and JNK2 were transiently activated by pressure overload, but only JNK1 was activated at the nuclei of cardiac myocytes. JNK1 activation was paralleled by phosphorylation of c-Jun at serine-63 in the myocardial nuclear fraction and by an increase in c-Jun expression in cardiac myocytes. A consistent increase in DNA binding of activator protein-1 (AP-1) complex was observed after 10 and 30 min of pressure overload and Supershift assays confirmed that c-Jun was a major component of activated AP-1 complex. Moreover, experiments performed with the specific JNK inhibitor SP-600125 abolished c-Jun phosphorylation and markedly attenuated its expression as well as the expression of the fetal gene -myosin heavy chain. Overall, these findings demonstrate a molecular basis for load-induced activation of c-Jun in cardiac myocytes and its connection with the regulation of fetal gene, characteristic of the acute response to pressure overload. (AU)

Processo FAPESP: 99/10263-0 - Sinalização celular durante aumento de tensão no coração: ativação e regulação de vias celulares de crescimento cardíaco
Beneficiário:Wilson Nadruz Junior
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 01/11698-1 - Mecanismos de sinalização celular ativados por sobrecarga mecânica: implicações na hipertrofia e remodelamento miocárdicos
Beneficiário:Kleber Gomes Franchini
Linha de fomento: Auxílio à Pesquisa - Temático