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

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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,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.

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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

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Philipps-Universität, Ketzerbach 63, D-35032, Marburg, Germany

    Stephanie Schwarz, Birgit Hufnagel & Josef Krieglstein

  2. Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität, Hittorfstraße 58-62, D-48149, Münster, Germany

    Melanie Dworak & Susanne Klumpp

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  1. Stephanie Schwarz
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  2. Birgit Hufnagel
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  3. Melanie Dworak
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  4. Susanne Klumpp
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  5. Josef Krieglstein
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Correspondence to Josef Krieglstein.

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Schwarz, S., Hufnagel, B., Dworak, M. et al. Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells. Apoptosis 11, 1111–1119 (2006). https://doi.org/10.1007/s10495-006-6982-1

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