Oxidative protein damage in cells engaged in beta-amyloidosis is related to apoE genotype.
The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease. The reduced antioxidant defense in epsilon4 carriers is suggested to contribute to beta-amyloidosis. We found that oxidative stress induced by treatment with Fe2+ ions raised more protein carbonyls in vascular smooth muscle cells isolated from human brains with apoE genotype epsilon4/epsilon4 than with 3epsilon/epsilon3 and epsilon3/epsilon4. Antioxidant vitamin E prevented formation of carbonyls but not in cells with genotype epsilon4/epsilon4. Treatment with Fe2+ ions induced cellular accumulation of amyloid-beta protein (Abeta)-immunoreactive material that co-localized with heme oxygenase, a marker of oxidative stress, and apoE. We hypothesize that the damage caused by oxidation in epsilon4/epsilon4 carriers facilitates development of beta-amyloidosis.
Mazur-Kolecka
Bozena
B
New York State Institute for Basic Research in Developmental Disabilities, Department of Pathological Neurobiology, 1050 Forest Hill Rd, Staten Island, NY 10314, USA.
Frackowiak
Janusz
J
Kowal
Dagmar
D
Krzeslowska
Jolanta
J
Dickson
Dennis
D
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics* / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D001057:Apolipoproteins E / Q000235:genetics*; D002478:Cells, Cultured; D005296:Ferrous Compounds / Q000009:adverse effects; D005838:Genotype; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001057:Apolipoproteins E; D005296:Ferrous Compounds