Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta

Effects of age and food restriction on oxidative DNA damage and antioxidant enzyme activities in the mouse aorta
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DOI:
10.1016/s0047-6374(01)00298-6
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发表时间:
2001-10-01
影响因子:
5.3
通讯作者:
Richardson, A
Richardson, A
中科院分区:
医学3区
文献类型:
--
作者:
Guo, ZM;Yang, H;Richardson, A

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在这项研究中,小鼠主动脉细胞的DNA损伤进行了测量使用彗星试验。与随意喂食的6月龄小鼠(Y-AL)相比,在将细胞与特异性识别氧化嘌呤的甲酰胺嘧啶-DNA糖基化酶(Fpg)、内切核酸酶III孵育后,从随意喂食的26月龄小鼠(O)获得的主动脉细胞中彗星测定的尾矩显著增加(Endo III),其特异性识别氧化的嘧啶,或Endo III和Fpg的组合。在将细胞与Endo III和Fpg的组合孵育后,与O-AL小鼠相比,从喂食限食饮食(O-FR)的26月龄小鼠获得的主动脉细胞中的尾矩显著降低。这些结果表明,氧化DNA损伤,即内III和Fpg敏感的网站,随着年龄的增长,在小鼠主动脉细胞和FR衰减的年龄相关的增加,氧化DNA损伤。为了确定小鼠主动脉细胞DNA氧化损伤的变化是否与这些细胞中的抗氧化状态有关,我们测定了小鼠主动脉中Cu/Zn-超氧化物歧化酶(SOD)、Mn-SOD、胞外-SOD、过氧化氢酶和谷胱甘肽过氧化物酶-1的活性。我们观察到,所研究的所有抗氧化酶的活性均随年龄的增加而显著增加,FR减弱了与年龄相关的增加。这些数据表明,在小鼠主动脉细胞中,与年龄相关的增加和FR诱导的氧化性DNA损伤的减少,即Endo III-和Fpg-敏感位点,不是由于抗氧化防御系统的改变。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
In this study, DNA damage in mouse aortic cells was measured using the comet assay. The tail moment of the comet assay in aortic cells obtained from 26-month-old mice fed ad libitum (O) was significantly increased as compared to 6-month-old mice fed ad libitum (Y-AL) after the cells were incubated with formamidopyrimidine-DNA glycosylase (Fpg), which specifically recognizes oxidized purines, endonuclease III (Endo III), which specifically recognizes oxidized pyrimidines, or the combination of Endo III and Fpg. The tail moment in aortic cells obtained from 26-month-old mice fed a food-restricted diet (O-FR) was significantly reduced as compared to O-AL mice after the cells were incubated with the combination of Endo III and Fpg. These results indicate that oxidative DNA lesions, i.e. the Endo III- and Fpg-sensitive sites, increase with age in mouse aortic cells and that FR attenuates the age-related increase in oxidative DNA damage. To determine if the changes in oxidative DNA damage in mouse aortic cells are related to the antioxidant status in these cells, we measured the activities of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, extracellular-SOD, catalase and glutathione peroxidase-1 in the mouse aorta, We observed that the activities of all antioxidant enzymes studied were significantly increased with age and that FR attenuated the age-related increase. These data indicate that the age-related increase and FR-induced decrease in oxidative DNA damage, i.e. the Endo III- and Fpg-sensitive sites, in mouse aortic cells is not due to alteration of the antioxidant defense system. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.