热量限制对衰老大鼠大脑碱基切除修复（BER）的影响。
Effect of caloric restriction on base-excision repair (BER) in the aging rat brain.
机构信息
Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, OR 97239, USA.
出版信息
Exp Gerontol. 2010 Mar;45(3):208-16. doi: 10.1016/j.exger.2009.12.003. Epub 2009 Dec 11.
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 approximately 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 beta 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.
摘要
脱嘌呤/脱嘧啶核酸内切酶（APE）是参与氧化 DNA 损伤碱基切除 DNA 修复（BER）途径的关键蛋白。使用新型寡核苷酸底物，我们证明在自由进食（AL）饮食的大鼠的额/顶叶皮质（F/PCTX）、小脑、脑干、中脑和下丘脑，APE 活性随年龄增长而下降。相比之下，年轻、热量限制（CR）大鼠的这些脑区的 APE 活性大约高 1.5-3 倍。尽管所有动物从六周大开始就持续接受 CR 治疗，但 CR 组的 APE 活性从中年开始下降，并持续到老年。然而，CR 使 APE 活性保持在一个水平，该水平在整个年龄段和所检查的脑区都显著高于 AL 大鼠。由于 CR 和 AL 大鼠 F/PCTX 中 APE、DNA 聚合酶β和 DNA 连接酶 III 的 Western 分析随年龄增长而保持不变，这表明 CR 大鼠中 APE 活性的增加是 APE 的差异翻译后修饰的结果。
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