Metformin prevented high glucose-induced endothelial reactive oxygen species via OGG1 in an AMPKα-Lin-28 dependent pathway

LIFE SCIENCES

卷:268

Article

Tao, Liangliang¹  Fan, Xiucai¹  Sun, Jin¹  Zhang, Zhu¹ 

[1] Nantong Univ, Jianhu Hosp, Dept Cardiol, Nantong, Peoples R China

关键词: Metformin;    8-Oxoguanine glycosylase;    Lin-28;    Reactive oxygen species;   

DOI  :  10.1016/j.lfs.2020.119015

来源: Elsevier

【 摘 要 】

Aims: Metformin improves vascular function in obese type 2 diabetic patients. 8-Oxoguanine glycosylase (OGG1) is a main DNA glycosylase that is involved in vascular complications in various diseases. However, whether metformin suppresses endothelial reactive species oxygen production via the OGG1 pathway is unclear. Main methods: Human umbilical vein endothelial cells (HUVECs) were exposed to HG (high glucose) with or without metformin. OGG1 and AMPKa levels were measured after metformin treatment, while HG-induced ROS were measured by a DHE probe. Key findings: Metformin reduced HG-induced endothelial ROS by upregulating OGG1. Additionally, OGG1 protein expression was dependent on its mRNA stability, which was reversed by genetic inhibition of AMPK alpha and Lin-28. Furthermore, the effect of OGG1 on HG-induced ROS was partially dependent on the AHR/Nrf2 pathway in HUVECs. Significance: These results suggested that metformin modulated HG-induced endothelial ROS via the AMPK alpha/Lin28/OGG1 pathway.

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