Oxidative stress after acute and chronic application of beta-amyloid fragment 25-35 in cortical cultures.
The aim of this work was to investigate whether free radical reactions play a role in beta-amyloid neurotoxicity. Rat cortical neurons were exposed acutely (24 h) or chronically (3, 7 days) to beta-amyloid biologically active fragment beta 25-35 (50 microM). In these conditions, where only the longest exposure induced neuronal death, superoxide dismutase activity was increased after acute exposure but no change was detected after chronic treatments, whereas a different pattern was observed for glutathione peroxidase. In the basal condition, there was an eight-fold increase in dichlorofluoroscein, used as peroxide production marker, in neuronal cells after 7 days treatment with beta 25-35. Moreover, the intracellular peroxide production induced by Fe2+/ascorbate stimulation was amplified by beta 25-35, increasingly up to 7 days of exposure, by which time the dichlorofluoroscein-stimulated levels were 33 times higher than in controls. In conclusion, our results show that oxidative stress and free radical production are linked to beta 25-35 exposure and may contribute to neurodegenerative events associated with beta-amyloid deposits in Alzheimer's disease.
Café
C
C
Institute of Pharmacology, University of Pavia, Italy.
Torri
C
C
Bertorelli
L
L
Angeretti
N
N
Lucca
E
E
Forloni
G
G
Marzatico
F
F
D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects*; D018384:Oxidative Stress; D051381:Rats; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor