Impact of apoE deficiency on oxidative insults and antioxidant levels in the brain.
Apolipoprotein E (apoE) is a lipid transport molecule, which has been linked to the pathogenesis of Alzheimer's disease. Recently we have demonstrated that the oxidative insults in hippocampus from AD patients were dependent on the apoE genotype. Interestingly, apoE protein concentration in hippocampus follows a genotype-dependent gradient with the lowest level occurring in varepsilon4 allele carrier. We raised the possibility that, in the hippocampus, the apoE level affects the oxidant/antioxidant balance. Here, we have examined in the apoE-deficient mouse the oxidant/antioxidant status in hippocampus and in frontal cortex from APOE-KO and wild-type mice at 3 and 13 months. We provided evidence that, in the hippocampus, the absence of apoE has a clear impact on the oxidant/antioxidant status. Endogenous level of thiobarbituric acid-reactive substances (TBARS) was found to be markedly elevated whereas level of alpha-tocopherol was decreased in APOE-deficient mice at 3 and 13 months. Superoxide dismutase activities were also lower in APOE-deficient mice at 13 months. Taken together, these data indicate that the steady state level of apoE may influence, to a certain extent, the balance between oxidants and antioxidants in hippocampus.
Ramassamy
C
C
Neuroscience Division, Douglas Hospital Research Center, Québec, Verdun, Canada.
Krzywkowski
P
P
Averill
D
D
Lussier-Cacan
S
S
Theroux
L
L
Christen
Y
Y
Davignon
J
J
Poirier
J
J
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D005625:Frontal Lobe / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D001057:Apolipoproteins E; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D013482:Superoxide Dismutase; D005978:Glutathione