Pro-atherogenic factors induce telomerase inactivation in endothelial cells through an Akt-dependent mechanism.
Advanced aging may contribute to impairment of angiogenesis and development of vascular diseases. Telomerase was shown to delay endothelial cell (EC) senescence. Therefore, we determined the regulation of telomerase activity in EC. Inhibition of phosphoinositol 3-kinase (PI3K) suppressed telomerase activity, whereas inhibitors directed against ERK1/2 or protein kinase C had no effect. Dominant negative Akt significantly reduced telomerase activity. Moreover, pro-atherogenic stimuli such as oxidized low density lipoprotein led to an inactivation of Akt and diminished telomerase activity. Thus, the PI3K/Akt pathway plays an important role in the regulation of telomerase activity. Pro-atherosclerotic factors impair telomerase activity and thereby may promote EC aging.
Division of Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
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Breitschopf
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Zeiher
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Dimmeler
D000375:Aging; D000818:Animals; D029681:Arabidopsis Proteins; D015153:Blotting, Western; D019556:COS Cells; D002417:Cattle; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology* / Q000201:enzymology*; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005799:Genes, Dominant; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010940:Plant Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000378:metabolism*; D012313:RNA; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014470:Umbilical Cord / Q000166:cytology
D029681:Arabidopsis Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D008077:Lipoproteins, LDL; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010940:Plant Proteins; D015221:Potassium Channels; D012313:RNA; D019098:Telomerase; C099252:oxidized low density lipoprotein; C422952:telomerase RNA; C074500:AKT1 protein, Arabidopsis