Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells
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- Schwarz, S., Hufnagel, B., Dworak, M. et al. Apoptosis (2006) 11: 1111. doi:10.1007/s10495-006-6982-1
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Unsaturated fatty acids with special structural features have been shown to activate serine/threonine protein phosphatase type 2C (PP2C) isoforms α and β 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 PP2Cα and PP2Cβ in SH-SY5Y cells or HUVECs, respectively. This downregulation was transient. Treatment of SH-SY5Y cells or HUVECs with oleic acid (18:1,cis-Δ9) 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.
KeywordsApoptosisFatty acidsHuman umbilical vein endothelial cellsOleic acidProtein phosphatase type 2CSH-SY5Y
bovine serum albumin
fetal calf serum
free fatty acids
human umbilical vein endothelial cells
phosphate buffered saline
protein phosphatase 1
protein phosphatase type 2A
protein phosphatase type 2C
protein phosphatase, magnesium-dependent
small interfering RNA
sodium dodecyl sulphate
Tris-buffered saline with Tween