Apoptosis

, Volume 11, Issue 7, pp 1111–1119

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

  • Stephanie Schwarz
  • Birgit Hufnagel
  • Melanie Dworak
  • Susanne Klumpp
  • Josef Krieglstein
Reports

DOI: 10.1007/s10495-006-6982-1

Cite this article as:
Schwarz, S., Hufnagel, B., Dworak, M. et al. Apoptosis (2006) 11: 1111. doi:10.1007/s10495-006-6982-1

Abstract

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,cis9) 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.

Keywords

ApoptosisFatty acidsHuman umbilical vein endothelial cellsOleic acidProtein phosphatase type 2CSH-SY5Y

Abbreviations

BSA

bovine serum albumin

DMSO

dimethylsulfoxide

ECL

enhanced chemoluminescence

FCS

fetal calf serum

FFAs

free fatty acids

HUVECs

human umbilical vein endothelial cells

PBS

phosphate buffered saline

PP1

protein phosphatase 1

PP2A

protein phosphatase type 2A

PP2C

protein phosphatase type 2C

PPM

protein phosphatase, magnesium-dependent

PPP

phosphoprotein phosphatase

RNAi

RNA interference

siRNA

small interfering RNA

SDS

sodium dodecyl sulphate

TBST

Tris-buffered saline with Tween

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Stephanie Schwarz
    • 1
  • Birgit Hufnagel
    • 1
  • Melanie Dworak
    • 2
  • Susanne Klumpp
    • 2
  • Josef Krieglstein
    • 1
  1. 1.Institut für Pharmakologie und ToxikologiePhilipps-UniversitätMarburgGermany
  2. 2.Institut für Pharmazeutische und Medizinische ChemieWestfälische Wilhelms-UniversitätMünsterGermany