This mini-review highlights the involvement of PP2C (protein phosphatase type 2C) family members α and β 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 PP2Cα and PP2Cβ in vitro induce apoptosis in various cell types as shown here for neurons and endothelial cells. Using RNA interference to reduce the amount of PP2Cα and PP2Cβ 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.

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