当前位置: X-MOL 学术Biochimie › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Potential effects of metformin in DNA BER system based on oxidative status in type 2 diabetes
Biochimie ( IF 3.9 ) Pub Date : 2018-08-08 , DOI: 10.1016/j.biochi.2018.08.002
Irem Dogan Turacli , Tuba Candar , Emine Berrin Yuksel , Sebnem Kalay , Ali Kemal Oguz , Selda Demirtas

Metformin is used to reduce hyperglycemia that induces energetic stress and leads to reduction in gluconeogenesis. Also, metformin inhibits complex I in oxidative phosphorylation, thereby decreasing cellular ATP levels. Activation of AMPK by the reduced ATP levels can induce inhibition of reactive oxygen species (ROS) production and activate p53-mediated DNA repair.

DNA polymerase-β and XRCC1 function to repair DNA damages in the BER (base excision repair) system. In type 2 diabetes patients, metformin can enhance AMPK activation therefore suppress oxidative stress. The changes on oxidative stress may alter p53's function and effect many cellular pathways such as; DNA repair. In our project we aim to understand the effects of metformin on p53 and DNA-BER system based on the oxidative status in type 2 diabetes patients.

Oxidative and antioxidative capacity, catalase, SOD, GPx activities and, DNA pol beta, XRCC1 and p53 levels were measured in metformin using or non-using type 2 diabetes patients and controls.

Metformin enhanced SOD and GPx activities in type 2 diabetes patients but the reflection of this increase to the total antioxidant capacity was not significant. Although the increase in DNA pol beta was not significant, XRCC1 and p53 levels were significantly upregulated with metformin treatment in type 2 diabetes patients. Our study reinforces the potential benefit of metformin in antioxidative capacity to protect cells from diabetic oxidative stress and in regulation of DNA BER system.



中文翻译:

基于氧化状态的二甲双胍在DNA BER系统中的潜在作用

二甲双胍可用于减少高血糖症,高血糖症可引起精力充沛的压力并导致糖异生减少。同样,二甲双胍可抑制复合物I的氧化磷酸化作用,从而降低细胞的ATP水平。通过降低的ATP含量激活AMPK可以诱导抑制活性氧(ROS)的产生并激活p53介导的DNA修复。

DNA聚合酶-β和XRCC1的功能是修复BER(碱基切除修复)系统中的DNA损伤。在2型糖尿病患者中,二甲双胍可以增强AMPK活化,因此可以抑制氧化应激。氧化应激的改变可能会改变p53的功能,并影响许多细胞途径,例如:DNA修复。在我们的项目中,我们旨在根据2型糖尿病患者的氧化状况来了解二甲双胍对p53和DNA-BER系统的影响。

在使用或不使用2型糖尿病的患者和对照组中,对二甲双胍中的氧化和抗氧化能力,过氧化氢酶,SOD,GPx活性以及DNA polβ,XRCC1和p53水平进行了测量。

二甲双胍增强了2型糖尿病患者的SOD和GPx活性,但这种增加对总抗氧化能力的反映并不显着。尽管DNA polβ的增加并不明显,但是在2型糖尿病患者中,二甲双胍治疗显着上调了XRCC1和p53的水平。我们的研究加强了二甲双胍在抗氧化能力方面的潜在优势,可以保护细胞免受糖尿病的氧化应激以及调节DNA BER系统。

更新日期:2018-08-08
down
wechat
bug