Role of endogenous RGS proteins on endothelial ERK 1/2 activation.
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 G(q) and G(i/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.
Anger
Thomas
T
Department for Cardiology, Friedrich-Alexander University of Erlangen, Germany. th.anger@arcor.de
Grebe
Nadine
N
Osinski
Daniela
D
Stelzer
Nadine
N
Carson
Walter
W
Daniel
Werner G
WG
Hoeher
Martin
M
Garlichs
Christoph D
CD
D050197:Atherosclerosis / Q000201:enzymology / Q000473:pathology; D002339:Carotid Arteries / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D003720:Densitometry; D042783:Endothelial Cells / Q000201:enzymology*; D004789:Enzyme Activation; D020868:Gene Silencing; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020710:RGS Proteins / Q000378:metabolism*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014471:Umbilical Veins / Q000166:cytology
D020710:RGS Proteins; D012330:RNA, Double-Stranded; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3