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Unsaturated fatty acids isolated from human lipoproteins activate protein phosphatase type 2Cbeta and induce apoptosis in endothelial cells |
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| Authors: | Hufnagel B Dworak M Soufi M Mester Z Zhu Y Schaefer J R Klumpp S Krieglstein J |
| Institution: | aDepartment for Pharmacology and Toxicology, Philipps-University Marburg, Ketzerbach 63, D-35032 Marburg, Germany bDepartment for Pharmaceutical and Medicinal Chemistry, Westphalian Wilhelms-University, Hittorfstraße 58–62, D-48149 Münster, Germany cDepartment of Internal Medicine-Cardiology, Philipps-University Marburg, Baldingerstrasse, D-35033 Marburg, Germany |
| Abstract: | Activity of serine/threonine protein phosphatase type 2C is known to be stimulated by certain unsaturated fatty acids and this enzyme dephosphorylates Bad, thus acting on apoptosis. This prompted us to investigate endothelial cell death. Here, we present evidence for the presence of protein phosphatase type 2Cβ (PP2Cβ) in human umbilical vein endothelial cells (HUVECs) and report on colocalization of PP2Cβ and Bad in the cytosol of endothelial cells. Lipophilic compounds that stimulated PP2Cβ activity in vitro were found to induce cell death of HUVECs. Lipoproteins did neither influence PP2Cβ activity nor affect cell behaviour. Lipoproteins treated with the lipoprotein lipase, however, stimulated the activity of PP2Cβ at least 10-fold concomitantly triggering cell death. Analytical methods revealed that both effects – stimulation of PP2Cβ and apoptosis – were caused by free fatty acids liberated from VLDL, LDL and HDL with oleic acid and linoleic acid as major constituents. The results provide novel insights in endothelial apoptosis and suggest that PP2Cβ participates in the development and progress of atherosclerosis. |
| Keywords: | Apoptosis Atherosclerosis Human umbilical vein endothelial cells Fatty acids Lipoproteins Protein phosphatase type 2C |
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