Role of endogenous RGS proteins on endothelial ERK 1/2 activation |
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Authors: | Anger Thomas Grebe Nadine Osinski Daniela Stelzer Nadine Carson Walter Daniel Werner G Hoeher Martin Garlichs Christoph D |
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Affiliation: | aDepartment for Cardiology, Friedrich-Alexander University of Erlangen, Germany;bDepartment for Cardiology, Klinikum Bayreuth, Germany |
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Abstract: | Endothelial cells are maintaining atherosclerotic signaling mediated by Extracellular Regulated Kinases 1 and 2 (ERK). Signaling gets activated upon stimulation of G protein-coupled receptors mediated by Gq and Gi/o proteins subjected to regulation by RGS proteins. The goal of the study was to delineate the specificity of RGS proteins modulating induced ERK phosphorylation. We used stimulated HUVEC, silenced specifically RGS proteins and compared assessed ERK 1/2 activation with immunohistochemical stainings on atherosclerotic plaques.Increased ERK phosphorylation was detected upon stimulation with Phenylephrine (2.6 ± 0.1 times over basal), Endothelin-1 (1.8 ± 0.2), Dopamine (5.1 ± 0.2), TNF (9.8 ± 0.7) or IL-4 (3.1 ± 0.3). RGS silencing increased activation of ERK 1/2: Phen (RGS3, 5), ET-1 (RGS3, 4), Dopa (RGS3), TNF (RGS2, 3, 4) or IL-4 (RGS2, 3, 4). Immunohistochemically, increased ERK activation was detected on atherosclerotic plaques.This data supports the role of RGS proteins on ERK activation in human atherosclerosis which identifies RGS proteins as new therapeutical targets. |
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Keywords: | Endogenous RGS proteins ERK-1/2 Atherosclerotic inflammation Endothelial cells Signal inhibition |
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