Base excision DNA repair levels in mitochondrial lysates of Alzheimer's disease.
Alzheimer's disease (AD) is a senile dementia with increased incidence in older subjects (age >65 years). One of the earliest markers of AD is oxidative DNA damage. Recently, it has been reported that preclinical AD patient brains show elevated levels of oxidative damage in both nuclear and mitochondrial nucleic acids. Moreover, different oxidative lesions in mitochondrial DNA are between 5- and 10-fold higher than in nuclear DNA in both control and AD postmortem brains. We previously showed that there is a significant loss of base excision repair (BER) components in whole tissue extracts of AD and mild cognitive impairment subjects relative to matched control subjects. However, comprehensive analysis of specific steps in BER levels in mitochondrial extracts of AD patient brains is not available. In this study, we mainly investigated various components of BER in mitochondrial extracts of AD and matched control postmortem brain samples. We found that the 5-hydroxyuracil incision and ligase activities are significantly lower in AD brains, whereas the uracil incision, abasic site cleavage, and deoxyribonucleotide triphosphate incorporation activities are normal in these samples.
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA.
Chandrika
C
Canugovi
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA.
Raghavendra A
RA
Shamanna
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA.
Deborah L
DL
Croteau
Laboratory of Molecular Gerontology, National Institute on Aging, Baltimore, MD, USA. Electronic address: vbohr@nih.gov.
Vilhelm A
VA
Bohr
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D004249:DNA Damage / Q000235:genetics*; D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D054306:Dideoxynucleotides / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism
D004272:DNA, Mitochondrial; D054306:Dideoxynucleotides; C045975:5-hydroxyuracil; D014498:Uracil; D011088:DNA Ligases
5-Hydroxyuracil; Alzheimer's disease; Base excision repair; Ligation; Mitochondria