Arachidonate metabolites affect the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein.
Amyloid precursor protein (APP) is degraded within the amyloid beta-protein (A beta) domain and its large soluble N-terminal fragment (secreted form of APP: APPs) is secreted into the culture media of many kinds of cells. We report here a quantitative increase in APPs secretion in the medium of human glioblastoma A172 cells grown under serum-free conditions. When A172 cells were treated with inhibitors of the arachidonate cascade, a modulation of APPs secretion was observed; the addition of small amounts of indomethacin increased secretory cleavage, but higher doses suppressed it. Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenases, also inhibited APPs secretion. These results suggest that arachidonate metabolites of the leukotriene pathway may promote APPs release upon extracellular signaling via a signal transduction pathway, while metabolites of the prostaglandin pathway inhibit APPs secretion.
Kinouchi
T
T
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Ono
Y
Y
Sorimachi
H
H
Ishiura
S
S
Suzuki
K
K
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism*; D002460:Cell Line; D003470:Culture Media; D016895:Culture Media, Serum-Free; D005909:Glioblastoma; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D015289:Leukotrienes / Q000378:metabolism; D009637:Masoprocol / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001095:Arachidonic Acids; D003470:Culture Media; D016895:Culture Media, Serum-Free; D015289:Leukotrienes; D011453:Prostaglandins; D009637:Masoprocol; D007213:Indomethacin