Endogenous mitochondrial oxidative stress in MnSOD-deficient mouse embryonic fibroblasts promotes mitochondrial DNA glycation.
Endogenous mitochondrial oxidative stress in MnSOD-deficient mouse embryonic fibroblasts promotes mitochondrial DNA glycation.
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DOI：
10.1016/j.freeradbiomed.2012.02.021
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发表时间：
2012-05-01
影响因子：
7.4
通讯作者：
Pischetsrieder, Monika
中科院分区：
文献类型：
--
作者：
Breyer, Viola;Weigel, Ingrid;Huang, Ting-Ting;Pischetsrieder, Monika
关键词：
由活性氧化物质（ROS）诱导的线粒体DNA（mtDNA）体细胞突变的积累被认为是衰老和与年龄相关的退行性疾病的主要原因。 ROS 还被证明可以促进蛋白质和 DNA 中某些高级糖基化终产物的形成，并且 N2-羧乙基-2'-脱氧鸟苷 (CEdG) 已被确定为主要的 DNA 结合 AGE。因此，在源自线粒体抗氧化酶锰超氧化物歧化酶（MnSOD）缺陷的突变小鼠（Sod2−/+）的原代胚胎成纤维细胞中研究了线粒体ROS对mtDNA糖化的影响。在Sod2-/+成纤维细胞与野生型成纤维细胞中，mtDNA的CEdG含量从1.90±1.39 pg/μg DNA增加至17.14±6.60 pg/μg DNA（p<0.001）。另一方面，Sod2+/+和-/+细胞之间核DNA的CEdG含量没有差异。类似地，Sod2+/+ 和 -/+ 之间的胞质蛋白在晚期糖基化终产物或蛋白质羰基含量方面没有表现出任何差异。综上所述，数据表明线粒体氧化应激特异性促进 mtDNA 糖化，并且不影响核 DNA 或胞浆蛋白。由于DNA糖化可以改变DNA完整性和基因功能，因此线粒体DNA糖化可能在线粒体功能衰退中发挥重要作用。
The accumulation of somatic mutations in mitochondrial DNA (mtDNA) induced by reactive oxidative species (ROS) is regarded as a major contributor of aging and age-related degenerative diseases. ROS has also been shown to facilitate the formation of certain advanced glycation end-products in proteins and DNAs, and N2-carboxyethyl-2′-deoxyguanosine (CEdG) has been identified as a major DNA-bound AGE. Therefore, the influence of mitochondrial ROS on the glycation of mtDNA was investigated in primary embryonic fibroblasts derived from mutant mice (Sod2−/+) deficient in the mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD). In Sod2−/+ fibroblasts vs. wildtype fibroblasts, the CEdG content of mtDNA was increased from 1.90±1.39 pg/μg DNA to 17.14±6.60 pg/μg DNA (p<0.001). On the other hand, the CEdG content of nuclear DNA did not differ between Sod2+/+ and −/+ cells. Similarly, cytosolic proteins did not show any difference in the advanced glycation end-products or protein carbonyl contents between Sod2+/+ and −/+. Taken together, the data suggest that mitochondrial oxidative stress specifically promotes glycation of mtDNA and does not affect nuclear DNA or cytosolic proteins. Because DNA glycation can change DNA integrity and gene functions, glycation of mtDNA may play an important role in the decline of mitochondrial functions.
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影响因子：
2.9
作者：
Benov, L
通讯作者：
Benov, L
影响因子：
7.4
作者：
Kelley, Eric E.;Khoo, Nicholas K. H.;Hundley, Nicholas J.;Malik, Umair Z.;Freeman, Bruce A.;Tarpey, Margaret M.
通讯作者：
Tarpey, Margaret M.
DOI：
10.1111/j.1749-6632.1999.tb07820.x
发表时间：
1999-01-01
期刊：
OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS
影响因子：
--
作者：
Huang, TT;Carlson, EJ;Epstein, CJ
通讯作者：
Epstein, CJ
影响因子：
5.3
作者：
Mansouri, A;Muller, FL;Van Remmen, H
通讯作者：
Van Remmen, H
影响因子：
3.1
作者：
Breyer, Viola;Becker, Cord-Michael;Pischetsrieder, Monika
通讯作者：
Pischetsrieder, Monika