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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.)

RhoA/ROCK signaling is critical to FAK activation by cyclic stretch in cardiac myocytes

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Autor(es):
Torsoni, Adriana S. ; Marin, Talita M. ; Velloso, Licio A. ; Franchini, Kleber G. [4]
Número total de Autores: 4
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 289, n. 4, p. H1488-H1496, Oct. 2005.
Área do conhecimento: Ciências da Saúde - Medicina
Assunto(s):Sistema cardiovascular   Miocárdio   Hipertrofia   Miócitos cardíacos   Proteína-tirosina quinases de adesão focal
Resumo

Focal adhesion kinase (FAK) has been shown to be activated in cardiac myocytes exposed to mechanical stress. However, details of how mechanical stimuli induce FAK activation are unknown. We investigated whether signaling events mediated by the RhoA/Rho-associated coiled coil-containing kinase (ROCK) pathway are involved in regulation of stretch-induced FAK phosphorylation at Tyr397 in neonatal rat ventricular myocytes (NRVMs). Immunostaining showed that RhoA localized to regions of myofilaments alternated with phalloidin (actin) staining. The results of coimmunoprecipitation assays indicated that FAK and RhoA are associated in nonstretched NRVMs, but cyclic stretch significantly reduced the amount of RhoA recovered from anti-FAK immunoprecipitates. Cyclic stretch induced rapid and sustained (up to 2 h) increases in phosphorylation of FAK at Tyr397 and ERK1/2 at Thr202/Tyr204. Blockade of RhoA/ROCK signaling by pharmacological inhibitors of RhoA (Clostridium botulinum C3 exoenzyme) or ROCK (Y-27632, 10 µmol/l, 1 h) markedly attenuated stretch-induced FAK and ERK1/2 phosphorylation. Similar effects were observed in cells treated with the inhibitor of actin polymerization cytochalasin D. Transfection of NRVMs with RhoA antisense oligonucleotide attenuated stretch-induced FAK and ERK1/2 phosphorylation and expression of -myosin heavy chain mRNA. Similar results were seen in cells transfected with FAK antisense oligonucleotide. These findings demonstrate that RhoA/ROCK signaling plays a crucial role in stretch-induced FAK phosphorylation, presumably by coordinating upstream events operationally linked to the actin cytoskeleton. (AU)

Processo FAPESP: 00/05137-4 - Avaliação da expressão localização e função de proteínas sinalizadoras com microscopia confocal
Beneficiário:Sara Teresinha Olalla Saad
Linha de fomento: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
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