Sinalização em miocitos cardiacos submetidos a aumentos de tensão

AUTOR(ES)
DATA DE PUBLICAÇÃO

2004

RESUMO

A variety of stimuli, such as hemodynamic overload, can lead to an increase in mechanical stress on cardiomyocytes that can be compensed by the development of a hypertrophyc phenotype. The hypertrophyc response is characterized by a rapid and coordinate activation of intracellular signaling pathways that regulate gene expression and results in a hypertrophyc growth of cardiac myocyte. The relative importance of each element that participate of signaling pathway and its contribution for the adaptative changes observed in cardiac myocyte in response to pressure overload, has been the focus of diverse researches. In the present study we investigated the Fak activation and subcellular localization in neonatal rat ventricular myocytes (NRVMs) submitted to pulsatile stretch, instead its participation in the atrial natriuretic factor (ANF) gene activation 5% to 20% (10-120 minute) pulsatile stretch of NRVMs lead to an increase of Fak phosphorylation at Tyr-397, as detected by phosphospecific antibody. This activation was accompanied by a change in Fak localization in NRVMs that, of the perinuclear regions in nonstretched cells change to aggregates regularly distributed along the myofilaments in stretched cells. Furthermore, a 4-hour cyclic stretch enhanced the activity of the ANF promoter-luciferase reporter gene. Disrupting endogenous FaklSrc signaling either by expression of a dominant-negative Fak mutant with phenylalanine substituted for Tyr-397 or by treatment with a c-Src pharmacological inhibitor markedly attenuated stretchinduced Fak activation and its redistribution at myofilaments and inhibited stretch-induced ANF gene activation...Note: The complete abstract is available with the full electronic digital thesis or dissertations

ASSUNTO(S)

celulas cultivadas miocitos cardiacos miocardio hipertrofia transdução de sinal

ACESSO AO ARTIGO

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