Amyloid beta enhances cytosolic phospholipase A2 level and arachidonic acid release via nitric oxide in APP-transfected PC12 cells
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 107166
Author(s) Chalimoniuk, Małgorzata; Stolecka, Anna; Cakała, Magdalena; Hauptmann, Susane; Schulz, Kris; Lipka, Uta; Leuner, Kristine; Eckert, Anne; Muller, Walter E; Strosznajder, Joanna B
Author(s) at UniBasel Eckert, Anne
Year 2007
Title Amyloid beta enhances cytosolic phospholipase A2 level and arachidonic acid release via nitric oxide in APP-transfected PC12 cells
Journal Acta biochimica Polonica
Volume 54
Number 3
Pages / Article-Number 611-23
Keywords amyloid beta, nitric oxide synthase, cytosolic phospholipase A(2), arachidonic acid, reactive oxygen species, antioxidative enzymes, calcium, mitochondria

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 beta (Abeta) 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 gamma-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 Abeta peptides enhance the protein level and phosphorylation of cPLA2 and AA release by the NO signaling pathway.

Publisher Państwowe Wydawnictwo Naukowe
ISSN/ISBN 0001-527X
Full Text on edoc No
PubMed ID
ISI-Number WOS:000249819500017
Document type (ISI) Journal Article

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