Base excision repair capacity in mitochondria and nuclei: tissue-specific variations
Base excision repair capacity in mitochondria and nuclei: tissue-specific variations
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DOI：
10.1096/fj.02-0463com
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发表时间：
2002-12-01
期刊：
影响因子：
4.8
通讯作者：
Bohr, VA
中科院分区：
文献类型：
--
作者：
Karahalil, B;Hogue, BA;Bohr, VA
碱基切除修复是DNA氧化损伤修复的主要途径。哺乳动物细胞必须在其核基因组和线粒体基因组中保持基因组的稳定性，这两个基因组对DNA损伤具有不同程度的脆弱性。这项研究对C57/BL6小鼠组织的线粒体和细胞核中的DNA糖基酶活性进行了定量，这些组织包括脑、肝脏、心脏、肌肉、肾脏和睾丸。用DNA损伤的寡核苷酸底物检测氧鸟嘌呤DNA糖基酶(OGG1)、尿嘧啶DNA糖基酶和核酸内切酶III同系物1(NTH1)的活性。线粒体含量归一化为柠檬酸合成酶活性，线粒体功能通过检测细胞色素C氧化酶(COX)活性来评估。在细胞核和线粒体提取液中，DNA糖基酶活性最高的是睾丸。大脑和心脏是氧化负荷最高的组织，其OGG1或NTH1活性水平并不高于肌肉或肾脏，后者是更多的糖酵解组织。一般而言，线粒体提取物的DNA糖基酶活性低于细胞核提取物。线粒体抽提物中的糖基酶活性与COX活性之间没有相关性，提示DNA修复酶可能受不同于线粒体酶的机制调控。
Base excision repair is the main pathway for repair of oxidative base lesions in DNA. Mammalian cells must maintain genomic stability in their nuclear and mitochondrial genomes, which have different degrees of vulnerability to DNA damage. This study quantifies DNA glycosylase activity in mitochondria and nucleus from C57/BL6 mouse tissues including brain, liver, heart, muscle, kidney, and testis. The activities of oxoguanine DNA glycosylase (OGG1), uracil DNA glycosylase, and endonuclease III homologue 1 (NTH1) were measured using oligonucleotide substrates with DNA lesions specific for each glycosylase. Mitochondrial content was normalized to citrate synthase activity and mitochondrial function was assessed by measuring cytochrome c oxidase (COX) activity. In nuclear and mitochondrial extracts, the highest DNA glycosylase activities were in testis. Brain and heart, tissues with the highest oxidative load, did not have higher levels of OGG1 or NTH1 activity than muscle or kidney, which are more glycolytic tissues. In general, mitochondrial extracts have lower DNA glycosylase activity than nuclear extracts. There was no correlation between glycosylase activities in the mitochondrial extracts and COX activity, suggesting that DNA repair enzymes may be regulated by a mechanism different from this mitochondrial enzyme.