Effect of caloric restriction on base-excision repair (BER) in the aging rat brain
Effect of caloric restriction on base-excision repair (BER) in the aging rat brain
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DOI：
10.1016/j.exger.2009.12.003
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发表时间：
2010-03-01
影响因子：
3.9
通讯作者：
Kow, Yoke W.
中科院分区：
文献类型：
--
作者：
Kisby, Glen E.;Kohama, Steven G.;Kow, Yoke W.
阿嘧啶/脱嘌呤核酸内切酶 (APE) 是参与氧化 DNA 损伤的碱基切除 DNA 修复 (BER) 途径的关键蛋白。使用一种新型寡核苷酸底物，我们证明了自由饮食 (AL) 饮食的大鼠额叶/顶叶皮层 (F/PCTX)、小脑、脑干、中脑和下丘脑中的 APE 活性随着年龄的增长而下降。相比之下，这些大脑区域的 APE 活性在年轻的热量限制 (CR) 大鼠中高出 1.5-3 倍。尽管所有动物从六周龄起就进行了持续的 CR 治疗，但 CR 组的 APE 活性在中年时开始下降，并持续到老年。然而，在不同年龄阶段和所检查的大脑区域中，CR 大鼠的 APE 活性均保持在显着高于 AL 大鼠的水平。由于 CR 和 AL 大鼠 F/PCTX 中 APE、DNA 聚合酶 0 和 DNA 连接酶 III 水平的 Western 分析随着年龄的增长而保持不变，这表明 CR 大鼠中 APE 活性增加是 APE 差异翻译后修饰的结果。 (C) 2009 Elsevier Inc. 保留所有权利。
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.