Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells

Unsaturated fatty acids with special structural features have been shown to activate serine/threonine protein phosphatase type 2C (PP2C) isoforms alpha and beta at physiological Mg2+-concentrations in vitro. These compounds also induce apoptosis in neuronal and endothelial cells. In this study we further analysed this striking correlation and tried to elucidate whether or not there is a causative relationship between activation of PP2C and induction of apoptosis. We employed RNA interference to simultaneously knock down PP2C alpha and PP2C beta in SH-SY5Y cells or HUVECs, respectively. This downregulation was transient. Treatment of SH-SY5Y cells or HUVECs with oleic acid (18:1, cis-Delta(9)) caused apoptosis in a time- and concentration-dependent manner. In both cases, cells with reduced PP2C-levels were less susceptible to oleic acid-induced cell damage. In conclusion, our results demonstrate that PP2C activation by unsaturated fatty acids actually causes apoptosis in neuronal and endothelial cells.