Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1911166 | Free Radical Biology and Medicine | 2008 | 13 Pages |
Abstract
Recent data support the role of oxidative stress in the pathogenesis of Alzheimer disease (AD). In particular, glutathione (GSH) metabolism is altered and its levels are decreased in affected brain regions and peripheral cells from AD patients and in experimental models of AD. In the past decade, interest in the protective effects of various antioxidants aimed at increasing intracellular GSH content has been growing. Because much experimental evidence suggests a possible protective role of unsaturated fatty acids in age-related diseases, we designed the synthesis of new S-acylglutathione (acyl-SG) thioesters. S-Lauroylglutathione (lauroyl-SG) and S-palmitoleoylglutathione (palmitoleoyl-SG) were easily internalized into the cells and they significantly reduced Aβ42-induced oxidative stress in human neurotypic SH-SY5Y cells. In particular, acyl-SG thioesters can prevent the impairment of intracellular ROS scavengers, intracellular ROS accumulation, lipid peroxidation, and apoptotic pathway activation. Palmitoleoyl-SG seemed more effective in cellular protection against Aβ-induced oxidative damage than lauroyl-SG, suggesting a valuable role for the monounsaturated fatty acid. In this study, we demonstrate that acyl-SG derivatives completely avoid the sharp lipoperoxidation in primary fibroblasts from familial AD patients occurring after exposure to Aβ42 aggregates. Hence, we put forward these derivatives as new antioxidant compounds which could be excellent candidates for therapeutic treatment of AD and other oxidative stress-related diseases.
Keywords
DTNBADDLCM-H2DCFDATNBMALDI/TOFAβ42PMSFSFAMUFATFAGSHHEPESPBSDMEMFBS3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide5,5′-dithio-bis(2-nitrobenzoic acid)DMSODulbecco's modified Eagle's mediumMTTN-(2-hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid)ROSAntioxidantsTrifluoroacetic acidsaturated fatty acidPolyunsaturated fatty acidmonounsaturated fatty acidPUFAAlzheimer diseaseOxidative stressBODIPYDimethyl sulfoxideFree radicalsfetal bovine serumAmyloid toxicityphenylmethylsulfonyl fluoridePhosphate-buffered salineMatrix-Assisted Laser Desorption/Ionization Time-of-Flighthigh-pressure liquid chromatographyHPLCGlutathioneReactive oxygen species
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Authors
Anna Pensalfini, Cristina Cecchi, Mariagioia Zampagni, Matteo Becatti, Fabio Favilli, Paolo Paoli, Serena Catarzi, Silvia Bagnoli, Benedetta Nacmias, Sandro Sorbi, Gianfranco Liguri,