Protein phosphatases types 2Calpha and 2Cbeta in apoptosis.
This mini-review highlights the involvement of PP2C (protein phosphatase type 2C) family members alpha and beta in apoptosis. The activity of these isoenzymes can be stimulated by unsaturated fatty acids with special structural features, e.g. oleic acid. Those fatty acids capable of activating PP2Calpha and PP2Cbeta in vitro induce apoptosis in various cell types as shown here for neurons and endothelial cells. Using RNA interference to reduce the amount of PP2Calpha and PP2Cbeta results in cells significantly less susceptible to the apoptotic effect of oleic acid. Increased endothelial cell death is considered to be an initial step of atherogenesis. Thus activation of PP2C by physiological unbound ('free') unsaturated fatty acids (liberated from lipoproteins) could represent a crucial mechanism in the development of atherosclerosis.
Klumpp
S
S
Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität, Münster, Germany. klumpp@uni-muenster.de
Thissen
M-C
MC
Krieglstein
J
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009410:Nerve Degeneration; D009474:Neurons / Q000473:pathology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010768:Phosphoserine / Q000378:metabolism; D000071636:Protein Phosphatase 2C; D013379:Substrate Specificity
D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D010768:Phosphoserine; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D008274:Magnesium