Apolipoprotein E deficiency promotes increased oxidative stress and compensatory increases in antioxidants in brain tissue.
The epsilon 4 allele of the apolipoprotein E gene (ApoE) is associated with Alzheimer's disease (AD). The extent of oxidative damage in AD brains correlates with the presence of the E4 allele of ApoE, suggesting an association between the ApoE4 genotype and oxygen-mediated damage in AD. We tested this hypothesis by subjecting normal and transgenic mice lacking ApoE to oxidative stress by folate deprivation and/or excess dietary iron. Brain tissue of ApoE-deficient mice displayed increased glutathione and antioxidant levels, consistent with attempts to compensate for the lack of ApoE. Folate deprivation and iron challenge individually increased glutathione and antioxidant levels in both normal and ApoE-deficient brain tissue. However, combined treatment with folate deprivation and dietary iron depleted antioxidant capacity and induced oxidative damage in ApoE-deficient brains despite increased glutathione, indicating an inability to compensate for the lack of ApoE under these conditions. These data support the hypothesis that ApoE deficiency is associated with oxidative damage, and demonstrate a combinatorial influence of genetic predisposition, dietary deficiency, and oxidative stress on oxidative damage relevant to AD.
Shea
Thomas B
TB
Center for Cellular Neurobiology and Neurodegeneration Research, University of Massachusetts at Lowell, Lowell, MA 01854, USA. thomas_shea@uml.edu
Rogers
Eugene
E
Ashline
David
D
Ortiz
Daniela
D
Sheu
Min-Shyan
MS
D000544:Alzheimer Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005494:Folic Acid Deficiency / Q000150:complications / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000975:Antioxidants; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D017392:Thiobarbituric Acid Reactive Substances; D007501:Iron; D005978:Glutathione