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

Changxing Shao; Shuling Xiong; Guo Min Li; Liya Gu; Guogen Mao; William R. Markesbery; Mark A. Lovell

doi:10.1016/j.freeradbiomed.2008.06.003

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

Changxing Shao, Shuling Xiong, Guo Min Li, Liya Gu, Guogen Mao, William R. Markesbery, Mark A. Lovell

Research output: Contribution to journal › Article › peer-review

102 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	813-819
Number of pages	7
Journal	Free Radical Biology and Medicine
Volume	45
Issue number	6
DOIs	https://doi.org/10.1016/j.freeradbiomed.2008.06.003
State	Published - Sep 15 2008

Bibliographical note

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.

Keywords

4-Hydroxynonenal
Alzheimer's disease
Lipid peroxidation
Mild cognitive impairment
Oxoguanine glycosylase

ASJC Scopus subject areas

Biochemistry
Physiology (medical)

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10.1016/j.freeradbiomed.2008.06.003

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

abstract = "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.",

keywords = "4-Hydroxynonenal, Alzheimer's disease, Lipid peroxidation, Mild cognitive impairment, Oxoguanine glycosylase",

author = "Changxing Shao and Shuling Xiong and Li, {Guo Min} and Liya Gu and Guogen Mao and Markesbery, {William R.} and Lovell, {Mark A.}",

note = "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. ",

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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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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