Amyloid beta protein (25-35) stimulation of phospholipases A, C and D activities of LA-N-2 cells.
[3H]Myristic acid prelabeled LA-N-2 cells were exposed to varying concentrations of amyloid beta protein (25-35), from 20 to 250 micrograms/ml, and the activation of phospholipases A and D estimated. A progressive increase in phosphatidylethanol formation, a measure of phospholipase D activity, and of free fatty acid release, a measure of phospholipase A activity, was observed over a time-course of 60 min. [3H]Inositol prelabeled LA-N-2 cells were exposed to varying concentrations of A beta P, from 20 to 125 micrograms/ml, and phospholipase C activation was measured. There was an increased release of inositol phosphates in the presence of amyloid beta protein as a function of incubation time. The effects of adrenergic, metabotropic amino acid and bombesin antagonists on the A beta P mediated stimulation of phospholipase C activity was investigated. Propranolol, a beta adrenergic antagonist, 7-chloro-kynurenic acid, a metabotropic amino acid antagonist, and [Tyr4-D-Phe12]bombesin, a bombesin antagonist, blunted the A beta P stimulation of phospholipase C activity in [3H]inositol prelabeled LA-N-2 cells. This suggests that amyloid beta protein activation of phospholipase C may be receptor mediated. The phospholipase C inhibitor U 71322 prevented the activation of phospholipase C by A beta P. However, this activation was not effected by tocopherol, propylgallate, or vitamin C.
Singh
I N
IN
Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.
McCartney
D G
DG
Kanfer
J N
JN
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D001839:Bombesin / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000032:analysis / Q000378:metabolism; D007700:Kinetics; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D007295:Inositol Phosphates; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D007294:Inositol; D011433:Propranolol; D010741:Phospholipases A; D010738:Type C Phospholipases; D010739:Phospholipase D; D001839:Bombesin