Effect of oxidative stress on DNA damage and beta-amyloid precursor proteins in lymphoblastoid cell lines from a Nigerian population.
The epsilon 4 allele of apolipoprotein E (APOE) is strongly associated with late-onset Alzheimer's disease (AD) in Caucasian populations, but our studies suggest that APOE epsilon 4 is not a risk factor for AD in Nigerian blacks and is a weak risk factor in African-Americans. The prevalence of AD is lower in Nigerians than in African-Americans. Increased oxidative damage to macromolecules in brain tissue by reactive oxygen species (ROS) has been reported in AD. Here we examined the effects of endogenous and induced oxidative stress on total (nuclear and mitochondrial) DNA damage in lymphoblastoid cell lines (5 probable AD and 3 controls) from Ibadan, Nigeria. Cells were exposed to 200 microM t-butyl peroxide (a generator of ROS) for 4 hours. Total DNA was isolated and digested with nuclease P1 and alkaline phosphatase. DNA fragments were separated by HPLC and the levels of 8-hydroxy-2'-deoxyguanosine (OH8dG, an indicator of DNA damage) and deoxyguanosine (dG) determined. We did not detect a significant difference in the OH8dG/dG ratio in untreated or treated cell lines in the two groups, and this was independent of APOE genotype. We also examined, by Western blotting, the level of beta-amyloid precursor protein (APP) which is involved in AD. The level of the heat shock protein (HSP-70) was examined as a control. There was a slight decrease in levels of APP and HSP-70 following treatment. Studies in cell lines from Caucasian subjects have shown an increase in mitochondrial DNA damage following oxidative challenge. Our preliminary results suggest that African populations are less vulnerable to chemical-induced oxidative DNA damage.
Lahiri
D K
DK
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202, USA. dlahiri@iupui.edu
Xu
Y
Y
Klaunig
J
J
Baiyewu
O
O
Ogunniyi
A
A
Hall
K
K
Hendrie
H
H
Sahota
A
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002460:Cell Line; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009549:Nigeria / Q000453:epidemiology; D018384:Oxidative Stress / Q000502:physiology*; D015995:Prevalence; D001741:Black or African American
D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D006360:Heat-Shock Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine