title: Differential efficacy of lipophilic and cytosolic antioxidants on generation of reactive oxygen species by amyloid-ß.
abstract: Exposure of neurons to amyloid-beta (Abeta) is accompanied by a cascade of oxidative damage that initiates with lipid peroxidation followed by subsequent generation of cytosolic free radicals and reactive oxygen species (ROS). The antioxidant vitamin E has been utilized to counteract Abeta-induced oxidative stress. We considered herein whether or not the lipid-solubility of vitamin E limits its neuroprotection to membrane-related oxidative damage, and renders it relatively ineffective where prior lipid peroxidation has already generated cytosolic free radicals and ROS. To test this possibility, we treated differentiated SH-SY-5Y human neuroblastoma with vitamin E or a cell-permeant antioxidant, N-acetyl cysteine (NAC), simultaneously with or 15 min after the application of Abeta. Both vitamin E and NAC prevented Abeta-induced ROS generation when applied simultaneously with Abeta, but only NAC prevented Abeta-induced ROS generation when added to cultures that had previously been exposed to Abeta. These results support the hypothesis that vitamin E can quench Abeta-induced lipid peroxidation, but cannot effectively quench ROS generated by prior lipid peroxidation. These findings in cell culture may provide limited insight into why vitamin E is not fully effective against neurodegeneration in AD in clinical settings, since some neuronal populations are likely to already have been compromised by prior Abeta exposure before vitamin E treatment was initiated.
authors.affiliation: Department of Biological Sciences, University of Massachusetts Lowell, Lowell MA 01854, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dhitavat
authors.forename: E R
authors.initials: ER
authors.lastname: Rivera
authors.forename: E
authors.initials: E
authors.lastname: Rogers
authors.forename: T B
authors.initials: TB
authors.lastname: Shea