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

被引:21
作者
Kisby, Glen E. [1 ]
Kohama, Steven G. [2 ]
Olivas, Antoinette [1 ]
Churchwell, Mona [3 ]
Doerge, Daniel [3 ]
Spangler, Edward [4 ]
de Cabo, Rafael [4 ]
Ingram, Donald K. [4 ]
Imhof, Barry [5 ]
Bao, Gaobin [5 ]
Kow, Yoke W. [5 ]
机构
[1] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97239 USA
[3] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA
[4] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA
[5] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA
关键词
Exonuclease; Apyrimidinic/apurinic endonuclease (APE); DNA polymerase beta; DNA ligase III; Frontal/parietal cortex; 8-Oxodeoxyguanosine; OXIDATIVE DNA-DAMAGE; SENESCENCE-ACCELERATED MICE; ALZHEIMERS-DISEASE; DIETARY RESTRICTION; MITOCHONDRIAL-DNA; GENOMIC STABILITY; AGE; STRESS; MOUSE; ENDONUCLEASE;
D O I
10.1016/j.exger.2009.12.003
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
030301 [社会学]; 100201 [内科学];
摘要
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 similar to 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 0 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. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:208 / 216
页数:9
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