FAK signalling mediates NF-κB activation by mechanical stress in cardiac myocytes

BackgroundNuclear Factor (NF)-κB and Focal Adhesion Kinase (FAK) signalling are implicated in cardiomyocyte hypertrophy. We investigated whether FAK signalling contributed towards NF-κB activation by mechanical stress in cardiac myocytes.MethodsExperiments were performed with pressure overload rat left ventricle and isolated cardiac myocytes from adult rats and isolated neonatal rat ventricular myocytes (NRVMs) underwent in vitro stretching.ResultsPressure overload induced NF-κB increase in myocardial cell nuclear extracts. Adult rat isolated cardiac myocyte confocal microscopy analysis showed NF-κB detected into nuclei. Cyclic stretch increased the amount and NF-κB DNA-binding activity in NRVMs nuclear extracts. NRVMs confocal microscopy confirmed NF-κB subcelullar relocation in stretched cells. Changes in NF-κB subcelular location and DNA-binding activity in stretched NRVMs were paralleled by increased FAK phosphorylation, detected in stretched NRVMs by anti-phosphospecific antibody directed to Tyr397. NRVMs treatment with FAK/Src pharmacological inhibitor attenuated NF-κB subcelullar relocation and increased DNA binding activity induced by cyclic stretch in cardiac myocytes.ConclusionsFAK signalling coordinates cardiac myocyte NF-κB activation in response to mechanical stress. Further studies are needed to elucidate the influence of this signalling pathway on gene transcription regulation, and cardiac myocyte phenotypic changes in response to mechanical stress.