TY - JOUR
T1 - Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain
AU - Shao, Changxing
AU - Xiong, Shuling
AU - Li, Guo Min
AU - Gu, Liya
AU - Mao, Guogen
AU - Markesbery, William R.
AU - Lovell, Mark A.
N1 - Funding Information:
Supported by NIH Grants 5-P01-AG05119 and 5-P30-AG028383, and by a grant from the Abercrombie Foundation. The authors thank Ms. Paula Thomason for technical and editorial assistance, and Ms. Sonya Anderson for subject demographic data.
PY - 2008/9/15
Y1 - 2008/9/15
N2 - 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.
AB - 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.
KW - 4-Hydroxynonenal
KW - Alzheimer's disease
KW - Lipid peroxidation
KW - Mild cognitive impairment
KW - Oxoguanine glycosylase
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U2 - 10.1016/j.freeradbiomed.2008.06.003
DO - 10.1016/j.freeradbiomed.2008.06.003
M3 - Article
C2 - 18598755
AN - SCOPUS:54949146482
SN - 0891-5849
VL - 45
SP - 813
EP - 819
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -