Alzheimer's amyloid beta-peptide associated free radicals increase rat embryonic neuronal polyamine uptake and ornithine decarboxylase activity: protective effect of vitamin E.
Recent evidence indicates that alterations in brain polyamine metabolism may be critical for nerve cell survival after a free radical initiated neurodegenerative process. It has been shown previously that A beta(1-42) and A beta(25-35) are toxic to neurons through a free radical dependent oxidative mechanism. Treatment of rat embryonic hippocampal neuronal cultures with A beta-peptides increased ornithine decarboxylase (ODC) activity and spermidine uptake, suggesting that oxidative stress upregulates the polyamine mechanism for the repair of free radical damage. Pretreatment of the cells with vitamin E prior to A beta exposure decreased ODC activity and spermidine uptake to control level. This study is the first to demonstrate that A beta treated cells show an increased polyamine metabolism in response to free radical mediated oxidative stress and that the free radical scavenger vitamin E prevents these attenuations. These results are discussed with reference to Alzheimer's disease.
Yatin
S M
SM
Department of Chemistry, Sanders-Brown Center of Aging, University of Kentucky, Lexington 40506-0055, USA.
Yatin
M
M
Aulick
T
T
Ain
K B
KB
Butterfield
D A
DA
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D005333:Fetus; D005609:Free Radicals / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013095:Spermidine / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D005609:Free Radicals; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D014810:Vitamin E; D009955:Ornithine Decarboxylase; D013095:Spermidine