Influence of various fatty acids on the activity of protein phosphatase type 2C and apoptosis of endothelial cells and macrophages.
In previous work we have demonstrated that protein phosphatase type 2C (PP2C) alpha and beta can be activated by mono-unsaturated fatty acids (MUFAs) leading to apoptosis of cultured endothelial cells. In the present paper we could show that saturated fatty acids (SFAs) did not activate PP2C and did not cause apoptosis both in endothelial cells and macrophages. However, long-chain SFAs (>16 C-atoms) were capable of inhibiting both, activation of PP2C as well as apoptosis of human umbilical vein endothelial cells (HUVECs) and macrophages caused by oleic acid. Interestingly, docosahexaenoic acid (DHA) known to protect arterial vessels against the progression of atherosclerosis caused apoptosis of HUVECs at high concentrations (200-400microM) but inhibited the apoptotic damage of HUVECs at a low, physiologically relevant concentration range (1-10microM). In contrast, oleic acid did not protect HUVECs against damage even at low concentrations (1-25microM). It is supposed that an unbalanced and chronically increased level of MUFAs in blood has an atherosclerotic potential. Furthermore, PP2C activated by MUFAs appears as a new target for drugs to prevent or treat atherosclerosis.
Krieglstein
Josef
J
Institut für Pharmakologie und Toxikologie, Philipps-Universitaet, Marburg, Germany. krieglst@uni-muenster.de
Hufnagel
Birgit
B
Dworak
Melanie
M
Schwarz
Stefanie
S
Kewitz
Tobias
T
Reinbold
Michael
M
Klumpp
Susanne
S
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006690:Bisbenzimidazole; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology*; D005227:Fatty Acids / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D019301:Oleic Acid / Q000494:pharmacology; D010078:Oxazines; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*
D005227:Fatty Acids; D005456:Fluorescent Dyes; D010078:Oxazines; C008619:Nile Blue; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D010749:Phosphoprotein Phosphatases; D006690:Bisbenzimidazole