8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle.
8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle.
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DOI：
10.1371/journal.pone.0181687
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sampath H
中科院分区：
文献类型：
--
作者：
Vartanian V;Tumova J;Dobrzyn P;Dobrzyn A;Nakabeppu Y;Lloyd RS;Sampath H
由内源性和外源性来源引起的氧化应激导致细胞组分的损伤，包括基因组和线粒体DNA。氧化性DNA损伤主要通过DNA糖基化酶启动的碱基切除修复途径修复。8-氧代鸟嘌呤DNA糖基化酶（OGG 1）识别并切割氧化的和环片段化的嘌呤，包括8-氧代鸟嘌呤，这是最常形成的氧化DNA损伤。缺乏OGG 1基因产物的小鼠容易出现代谢综合征的多种特征，包括高脂饮食诱导的肥胖、肝脂肪变性和胰岛素抵抗。在这里，我们报告说，OGG 1缺陷小鼠也显示骨骼肌病理，包括增加肌肉脂质沉积和改变基因调节骨骼肌中的脂质摄取和线粒体分裂。此外，TCA循环和碳水化合物和脂质代谢的基因的表达也显着改变OGG 1缺陷小鼠的肌肉。这些组织变化伴随着OGG 1缺陷动物肌肉功能标志物的显著降低，包括握力和跑步机耐力下降。总的来说，这些数据表明骨骼肌OGG 1在维持最佳组织功能中的作用。
Oxidative stress resulting from endogenous and exogenous sources causes damage to cellular components, including genomic and mitochondrial DNA. Oxidative DNA damage is primarily repaired via the base excision repair pathway that is initiated by DNA glycosylases. 8-oxoguanine DNA glycosylase (OGG1) recognizes and cleaves oxidized and ring-fragmented purines, including 8-oxoguanine, the most commonly formed oxidative DNA lesion. Mice lacking the OGG1 gene product are prone to multiple features of the metabolic syndrome, including high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Here, we report that OGG1-deficient mice also display skeletal muscle pathologies, including increased muscle lipid deposition and alterations in genes regulating lipid uptake and mitochondrial fission in skeletal muscle. In addition, expression of genes of the TCA cycle and of carbohydrate and lipid metabolism are also significantly altered in muscle of OGG1-deficient mice. These tissue changes are accompanied by marked reductions in markers of muscle function in OGG1-deficient animals, including decreased grip strength and treadmill endurance. Collectively, these data indicate a role for skeletal muscle OGG1 in the maintenance of optimal tissue function.
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影响因子：
14.9
作者：
Bess AS;Crocker TL;Ryde IT;Meyer JN
通讯作者：
Meyer JN
影响因子：
--
作者：
Cardozo-Pelaez, F;Cox, DP;Bolin, C
通讯作者：
Bolin, C
影响因子：
4.8
作者：
Dobrzyn, A;Dobrzyn, P;Ntambi, JM
通讯作者：
Ntambi, JM
影响因子：
12.7
作者：
Fukae, J;Takanashi, M;Hattori, N
通讯作者：
Hattori, N
影响因子：
5.3
作者：
Jheng, Huei-Fen;Tsal, Pei-Jane;Tsai, Yau-Sheng
通讯作者：
Tsai, Yau-Sheng