Aging increases amyloid beta-peptide-induced 8-iso-prostaglandin F2alpha release from rat brain.
In order to investigate whether amyloid beta-peptide-induced oxidative damage in the brain could be related to aging, we studied the release of 8-iso-prostaglandin (PG)F2alpha, a stable marker of cellular oxidative stress, in brain synaptosomes from Wistar rats of different ages (3, 6, 12, 18 months old), both basally and after amyloid beta-peptide (1-40) perfusion. We found that basal release of 8-iso-PGF2alpha was not significantly different among all age groups of rats. Either phospholipase A2 activation induced by calcium ionophore A23187 (10 nM) or amyloid beta-peptide (5 microM) did not modify isoprostane release, when these substances were used alone. In contrast, amyloid beta-peptide (1-5 microM) preincubation caused a dose-dependent increase of A23187-stimulated 8-iso-PGF2alpha release in each age group, which was also strikingly correlated to aging of rats. Furthermore, ferric ammonium sulfate stimulates isoprostane production to levels comparable to those induced by amyloid beta-peptide. In conclusion, although 8-iso-PGF2alpha production from rat brain synaptosomes is independent from aging in the basal state, aging renders neurons more vulnerable to amyloid beta-peptide-induced oxidative toxicity.
Brunetti
Luigi
L
Department of Drug Sciences, School of Pharmacy, G. D'Annunzio University, via dei Vestini, 66013 Chieti, Italy.
Michelotto
Barbara
B
Orlando
Giustino
G
Recinella
Lucia
L
Di Nisio
Chiara
C
Ciabattoni
Giovanni
G
Vacca
Michele
M
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D028441:F2-Isoprostanes / Q000378:metabolism*; D005290:Ferric Compounds / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D000685:Serum Amyloid A Protein / Q000378:metabolism / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects; D013997:Time Factors
D028441:F2-Isoprostanes; D005290:Ferric Compounds; D007476:Ionophores; D000685:Serum Amyloid A Protein; C075750:8-epi-prostaglandin F2alpha; D000001:Calcimycin; D015237:Dinoprost; C049467:ammonium ferric sulfate