Effect of caloric restriction on base-excision repair (BER) in the aging rat brain

Glen E. Kisby; Steven G. Kohama; Antoinette Olivas; Mona Churchwell; Daniel Doerge; Edward Spangler; Rafael de Cabo; Donald K. Ingram; Barry Imhof; Gaobin Bao; Yoke W. Kow

doi:10.1016/j.exger.2009.12.003

Effect of caloric restriction on base-excision repair (BER) in the aging rat brain

Glen E. Kisby, Steven G. Kohama, Antoinette Olivas, Mona Churchwell, Daniel Doerge, Edward Spangler, Rafael de Cabo, Donald K. Ingram, Barry Imhof, Gaobin Bao, Yoke W. Kow

Oregon National Primate Research Center

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

24 Scopus citations

Abstract

Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was ∼1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase β and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE.

Original language	English (US)
Pages (from-to)	208-216
Number of pages	9
Journal	Experimental Gerontology
Volume	45
Issue number	3
DOIs	https://doi.org/10.1016/j.exger.2009.12.003
State	Published - Mar 2010

Keywords

8-Oxodeoxyguanosine
Apyrimidinic/apurinic endonuclease (APE)
DNA ligase III
DNA polymerase β
Exonuclease
Frontal/parietal cortex

ASJC Scopus subject areas

Biochemistry
Aging
Molecular Biology
Genetics
Endocrinology
Cell Biology

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10.1016/j.exger.2009.12.003

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title = "Effect of caloric restriction on base-excision repair (BER) in the aging rat brain",

abstract = "Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was ∼1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase β and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE.",

keywords = "8-Oxodeoxyguanosine, Apyrimidinic/apurinic endonuclease (APE), DNA ligase III, DNA polymerase β, Exonuclease, Frontal/parietal cortex",

author = "Kisby, {Glen E.} and Kohama, {Steven G.} and Antoinette Olivas and Mona Churchwell and Daniel Doerge and Edward Spangler and Cabo, {Rafael de} and Ingram, {Donald K.} and Barry Imhof and Gaobin Bao and Kow, {Yoke W.}",

note = "Funding Information: We thank Dr. Vilhelm Bohr for his valuable comments on the manuscript. This work is supported by NIH CA90860 (YWK), NIEHS PO1 ES011163 (YWK), RR00163 (SGK) and DAMD 17-98-1-8625 (GK).",

year = "2010",

month = mar,

doi = "10.1016/j.exger.2009.12.003",

language = "English (US)",

volume = "45",

pages = "208--216",

journal = "Experimental Gerontology",

issn = "0531-5565",

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T1 - Effect of caloric restriction on base-excision repair (BER) in the aging rat brain

AU - Kisby, Glen E.

AU - Kohama, Steven G.

AU - Olivas, Antoinette

AU - Churchwell, Mona

AU - Doerge, Daniel

AU - Spangler, Edward

AU - Cabo, Rafael de

AU - Ingram, Donald K.

AU - Imhof, Barry

AU - Bao, Gaobin

AU - Kow, Yoke W.

N1 - Funding Information: We thank Dr. Vilhelm Bohr for his valuable comments on the manuscript. This work is supported by NIH CA90860 (YWK), NIEHS PO1 ES011163 (YWK), RR00163 (SGK) and DAMD 17-98-1-8625 (GK).

PY - 2010/3

Y1 - 2010/3

N2 - Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was ∼1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase β and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE.

AB - Apyrimidinic/apurinic endonuclease (APE) is a key protein involved in the base-excision DNA repair (BER) pathway of oxidative DNA lesions. Using a novel oligonucleotide substrate, we demonstrate that APE activity in the frontal/parietal cortex (F/PCTX), cerebellum, brainstem, midbrain and hypothalamus declined with age in rats on an ad libitum (AL) diet. In contrast, APE activity for these brain regions was ∼1.5-3 times higher in young, caloric restricted (CR) rats. Despite continuous CR treatment in all animals since six weeks of age, APE activity in the CR group started to decline by middle-age and continued into old age. However, CR maintained APE activity at a level that was significantly higher than that in AL rats across age and in the brain regions examined. Because Western analysis of APE, DNA polymerase β and DNA ligase III levels in the F/PCTX of both CR and AL rats remained unchanged with age, this suggests that the increased APE activity in CR rats is the result of differential post-translational modification of APE.

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KW - Apyrimidinic/apurinic endonuclease (APE)

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Effect of caloric restriction on base-excision repair (BER) in the aging rat brain

Abstract

Keywords

ASJC Scopus subject areas

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