Effect of zinc ions on the cytotoxicity induced by the amyloid beta-peptide.
Insoluble aggregates of the amyloid beta-peptide (A beta) are a major constituent of senile plaques found in brains of Alzheimer's disease patients. The beta-amyloid fragment A beta(1-40) is toxic to rat pheochromocytoma PC12 cells, leading to a concentration-dependent decrease in the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The detrimental effects of A beta(1-40) are enhanced in the presence of 1 mM zinc, whereas 50 microM zinc exerts a protective effect against A beta(1-40)-induced toxicity. Exposure of PC12 cells to low zinc concentrations (50 microM) affords a decrease (1.4-fold) in the extent of lipid peroxidation, a decrement in protein oxidation (1.1-fold), and an increase in ATP levels (1.2-fold), although the differences were not statistically significant. However, treatment of cells with high concentrations of zinc (1 mM) led to significant increases in lipid peroxidation (3.7-fold) and protein oxidation (1.5-fold) and to depletion of the ATP pool (21-fold). These data suggest that zinc has a concentration-dependent dual effect, protective and toxic, thus playing an important role in the pathogenesis of Alzheimer's disease.
Moreira
P
P
Center for Neuroscience of Coimbra, Faculty of Medicine and Department of Zoology, University of Coimbra, Portugal.
Pereira
C
C
Santos
M S
MS
Oliveira
C
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002244:Carbon / Q000378:metabolism; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007477:Ions; D015227:Lipid Peroxidation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D015032:Zinc / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D007477:Ions; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D002244:Carbon; D000255:Adenosine Triphosphate; D015032:Zinc; D010100:Oxygen