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• W2114555592 abstract "Myocardial stretch activates a number of interconnected pathways including the protein kinase C (PKC) pathway that in turn activates mitogen activated protein kinases (MAPK), leading to gene expression stimulation and ventricular hypertrophy. A role of calcineurin has also been shown during hypertrophy. The goal of our study was to look for a possible interconnection between PKC and calcineurin in myocardial stretch.Neonatal rat cardiomyocytes were cultured for 5 days and a 15% stretch was applied. Expression of MAPK and PKC-epsilon was evaluated by Western blot analysis. The specific role of PKC-epsilon was evaluated by transfection of cardiomyocytes with a specific inhibitor peptide. Calcineurin and PKC-epsilon complex formation and co-localization were evaluated by co-immunoprecipitation and by immunolocalization.The PKC isoform involved in stretch-induced ERK and JNK activations was PKC-epsilon. We show here that calcineurin is also found to be involved in the stretch response and that calcineurin and PKC-epsilon co-operate at 2 levels during stretch. First, stretch-induced translocation of PKC-epsilon from the cytosolic to the membrane fraction was inhibited by calcineurin inhibitors, indicating that calcineurin was necessary for PKC-epsilon activation induced by stretch. A second level of interaction was the formation of a calcineurin-PKC-epsilon complex, which increased during stretch. Immunofluorescent studies indicated that, after stretch, calcineurin and PKC-epsilon were co-localized at the level of the perinuclear membrane. These results may have a major relevance in vivo since we also found similar PKC-epsilon-calcineurin complexes in the phase of thoracic aortic stenosis in rats during which heart failure develops.Calcineurin appears to be necessary for stretch-induced PKC-epsilon activation after which the phosphatase and the kinase are co-localized in a complex at the level of the perinuclear membrane where they may finely regulate the phosphorylation of their target proteins." @default.
• W2114555592 created "2016-06-24" @default.
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• W2114555592 date "2006-07-01" @default.
• W2114555592 modified "2023-10-12" @default.
• W2114555592 title "Dual level of interactions between calcineurin and PKC-ε in cardiomyocyte stretch" @default.
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• W2114555592 doi "https://doi.org/10.1016/j.cardiores.2006.03.012" @default.
• W2114555592 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16682016" @default.
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