Amyloid beta enhances cytosolic phospholipase A2 level and arachidonic acid release via nitric oxide in APP-transfected PC12 cells

• Authors: Małgorzata Chalimoniuk , Anna Stolecka , Magdalena Cąkała , Susane Hauptmann , Kris Schulz , Uta Lipka , Kristine Leuner , Anne Eckert , Walter E Muller , Joanna B. Strosznajder
• Languages of publication: EN

Abstracts

EN

Cytosolic phospholipase A2 (cPLA2) preferentially liberates arachidonic acid (AA), which is known to be elevated in Alzheimer's disease (AD). The aim of this study was to investigate the possible relationship between enhanced nitric oxide (NO) generation observed in AD and cPLA2 protein level, phosphorylation, and AA release in rat pheochromocytoma cell lines (PC12) differing in amyloid beta secretion. PC12 control cells, PC12 cells bearing the Swedish double mutation in amyloid beta precursor protein (APPsw), and PC12 cells transfected with human APP (APPwt) were used. The transfected APPwt and APPsw PC12 cells showed an about 2.8- and 4.8-fold increase of amyloid β (Aβ) secretion comparing to control PC12 cells. An increase of NO synthase activity, cGMP and free radical levels in APPsw and APPwt PC12 cells was observed. cPLA2 protein level was higher in APPsw and APPwt PC12 cells comparing to PC12 cells. Moreover, phosphorylated cPLA2 protein level and [3H]AA release were also higher in APP-transfected PC12 cells than in the control PC12 cells. An NO donor, sodium nitroprusside, stimulated [3H]AA release from prelabeled cells. The highest NO-induced AA release was observed in control PC12 cells, the effect in the other cell lines being statistically insignificant. Inhibition of cPLA2 by AACOCF3 significantly decreased the AA release. Inhibitors of nNOS and γ-secretase reduced AA release in APPsw and APPwt PC12 cells. The basal cytosolic [Ca2+]i and mitochondrial Ca2+ concentration was not changed in all investigated cell lines. Stimulation with thapsigargin increased the cytosolic and mitochondrial Ca2+ level, activated NOS and stimulated AA release in APP-transfected PC12 cells. These results indicate that Aβ peptides enhance the protein level and phosphorylation of cPLA2 and AA release by the NO signaling pathway.

Keywords

EN

nitric oxide synthase; amyloid beta; calcium; arachidonic acid; antioxidative enzymes; reactive oxygen species; cytosolic phospholipase A_2; mitochondria

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 3
• Pages: 611-623

Dates

published

2007

received

2007-02-02

revised

2007-04-27

accepted

2007-07-17

(unknown)

2007-08-23

Contributors

author

Małgorzata Chalimoniuk

• Medical Research Center, Department of Cellular Signaling, Polish Academy of Sciences Warszawa, Warszawa, Poland

author

Anna Stolecka

• Academy of Physical Education, Department of Physiology, Katowice, Poland

author

Magdalena Cąkała

• Medical Research Center, Department of Cellular Signaling, Polish Academy of Sciences Warszawa, Warszawa, Poland

author

Susane Hauptmann

• Academy of Physical Education, Department of Physiology, Katowice, Poland

author

Kris Schulz

• Academy of Physical Education, Department of Physiology, Katowice, Poland

author

Uta Lipka

• Academy of Physical Education, Department of Physiology, Katowice, Poland

author

Kristine Leuner

• Academy of Physical Education, Department of Physiology, Katowice, Poland

author

Anne Eckert

• Neurobiology Research Laboratory, Psychiatric University Clinic, Basel, Switzerland

author

Walter E Muller

• Academy of Physical Education, Department of Physiology, Katowice, Poland

author

Joanna B. Strosznajder

• Medical Research Center, Department of Cellular Signaling, Polish Academy of Sciences Warszawa, Warszawa, Poland

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