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

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. Human umbilical vein endothelial cells (HUVECs) were exposed to HG (high glucose) with or without metformin. OGG1 and AMPKα levels were measured after metformin treatment, while HG-induced ROS were measured by a DHE probe. 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 AMPKα and Lin-28. Furthermore, the effect of OGG1 on HG-induced ROS was partially dependent on the AHR/Nrf2 pathway in HUVECs. These results suggested that metformin modulated HG-induced endothelial ROS via the AMPKα/Lin-28/OGG1 pathway.