Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain

Eight-hydroxy-2′-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer's disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activi...

Full description

Saved in:
Bibliographic Details
Published inFree radical biology & medicine Vol. 45; no. 6; pp. 813 - 819
Main Authors Shao, Changxing, Xiong, Shuling, Li, Guo-Min, Gu, Liya, Mao, Guogen, Markesbery, William R., Lovell, Mark A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.09.2008
Subjects
4-Hydroxynonenal
Alzheimer Disease - enzymology
Alzheimer's disease
Blotting, Western
Brain - enzymology
Cell Nucleus - enzymology
Cognition Disorders - enzymology
DNA Glycosylases - metabolism
Female
Humans
Immunoprecipitation
Lipid peroxidation
Male
Mild cognitive impairment
Mitochondria - enzymology
Oxoguanine glycosylase
Polymorphism, Single-Stranded Conformational
PBS
AD
4-Hydroxynonenal
DTT
Mild cognitive impairment
FL
OGG1
Lipid peroxidation
PMI
BER
LAD
CER
SDS-PAGE
MCI
NC
ROS
TL
PL
NFT
Alzheimer's disease
HNE
Oxoguanine glycosylase
8-OHdG
Online AccessGet full text

Cover

More Information
Summary:Eight-hydroxy-2′-deoxyguanosine (8-OHdG) is increased in the brain in late-stage Alzheimer's disease (LAD) and mild cognitive impairment (MCI). To determine if decreased base-excision repair contributes to these elevations, we measured oxoguanine glycosylase 1 (OGG1) protein and incision activities in nuclear and mitochondrial fractions from frontal (FL), temporal (TL), and parietal (PL) lobes from 8 MCI and 7 LAD patients, and 6 age-matched normal control (NC) subjects. OGG1 activity was significantly ( P < 0.05) decreased in nuclear specimens of FL, TL, and PL in MCI and LAD and in mitochondria from LAD FL and TL and MCI TL. Nuclear OGG1 protein was significantly decreased in LAD FL and MCI and LAD PL. No differences in mitochondrial OGG1 protein levels were found. Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2008.06.003