title: Aging increases amyloid beta-peptide-induced 8-iso-prostaglandin F2alpha release from rat brain.
abstract: 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.
authors.affiliation: Department of Drug Sciences, School of Pharmacy, G. D'Annunzio University, via dei Vestini, 66013 Chieti, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
authors.forename: Barbara
authors.initials: B
authors.lastname: Michelotto
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.forename: Lucia
authors.initials: L
authors.lastname: Recinella
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Nisio
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciabattoni
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
mesh_terms: 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
chemical_list: 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