Unsaturated fatty acids isolated from human lipoproteins activate protein phosphatase type 2Cbeta and induce apoptosis in endothelial cells.
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 2Cbeta (PP2Cbeta) in human umbilical vein endothelial cells (HUVECs) and report on colocalization of PP2Cbeta and Bad in the cytosol of endothelial cells. Lipophilic compounds that stimulated PP2Cbeta activity in vitro were found to induce cell death of HUVECs. Lipoproteins did neither influence PP2Cbeta activity nor affect cell behaviour. Lipoproteins treated with the lipoprotein lipase, however, stimulated the activity of PP2Cbeta at least 10-fold concomitantly triggering cell death. Analytical methods revealed that both effects - stimulation of PP2Cbeta 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 PP2Cbeta participates in the development and progress of atherosclerosis.
Hufnagel
B
B
Department for Pharmacology and Toxicology, Philipps-University Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
Dworak
M
M
Soufi
M
M
Mester
Z
Z
Zhu
Y
Y
Schaefer
J R
JR
Klumpp
S
S
Krieglstein
J
J
D017209:Apoptosis; D001161:Arteriosclerosis / Q000503:physiopathology*; D018929:Cell Culture Techniques; D002784:Cholesterol / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology; D005227:Fatty Acids / Q000502:physiology*; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D014471:Umbilical Veins / Q000166:cytology
D005227:Fatty Acids; D008074:Lipoproteins; D002784:Cholesterol; D008071:Lipoprotein Lipase; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C