Discussion of the role of the extracellular signal-regulated kinase-phospholipase A2 pathway in production of reactive oxygen species in Alzheimer's disease.
In this paper we show that exposure of a rat brain synaptosome fraction to the amyloid beta peptide fragment betaA(25-35), but not the inverted peptide betaA(35-25), stimulated production of reactive oxygen species (ROS) in a concentration- and time-dependent manner. The ROS formation was attenuated by the tyrosine kinase inhibitor genistein, the mitogen-activated protein kinase inhibitor U0126, and the phospholipase A2 (PLA2) inhibitor 7,7-dimethyl-(5Z,8Z)-eicosadienoic acid. This strongly suggests that betaA(25-35) stimulated ROS production through an extracellular signal-regulated kinase-PLA2-dependent pathway. The interaction between these enzymes and their possible involvement in free radical formation in Alzheimer's disease are discussed.
Andersen
Jannike M
JM
Norwegian Defence Research Establishment, Division for Protection and Materiel, PO Box 25, N-2027 Kjeller, Norway. jannike.andersen@ffi.no
Myhre
Oddvar
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Fonnum
Frode
F
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D016229:Amyloid beta-Peptides; D002070:Butadienes; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D009570:Nitriles; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C113580:U 0126; C113041:amyloid beta-protein (35-25); C059778:7,7-dimethyl-5,8-eicosadienoic acid; D019833:Genistein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010741:Phospholipases A; D054467:Phospholipases A2