High glucose induced endothelial cell reactive oxygen species via OGG1/PKC/NADPH oxidase pathway.

Abstract

AIMS:

Reactive oxygen species (ROS) caused by high glucose (HG) is involved in a lot of diseases including diabetes. However, the underlying mechanism of ROS induction by HG remains unclear. Emerging evidence has shown the 8-oxoguanine glycosylase (OGG1) is the main DNA glycosylase responsible for atherosclerosis, obesity, hepatic steatosis, and insulin resistance, and so on. Our aim was to explore the role of OGG1 on HG-mediated endothelial ROS.

MAIN METHODS:

Human umbilical vein endothelial cells (HUVECs) were exposed to HG (30 mM) for different time periods. HG predominantly inhibited OGG1 expression in a time-dependent manner measured by western blotting, qPCR and immunofluorescence. Additionally, HUVECs were cultured with a fluorescent probe, DCFH and DHE, after being subjected to HG. Cell chemiluminescence and flow cytometry results revealed that HG caused endothelial ROS activation.

KEY FINDINGS:

High glucose remarkably decreased endothelial OGG1 expression. The overexpression of OGG1 significantly reversed HG-mediated PKC and NADPH oxidase activities and ROS levels. Moreover, manipulated expression of PKC significantly contacted the role of OGG1 on NADPH oxidase activation.

SIGNIFICANCE:

These results suggest that OGG1 downregulation promoted HG-induced endothelial ROS production and might be a potential clinical treatment target of diabetics.

• Authors: Xiangrong Xie, Yan Chen, Jichun Liu, Wenbo Zhang, Xuan Zhang, Lintao Zha, Wenjie Liu, Yang Ling, Shu Li, Shengxing Tang
• Journal: Life sciences (Life Sci) Vol. 256 Pg. 117886 (Sep 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 32497631 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Reactive Oxygen Species
• NADPH Oxidases
• Protein Kinase C
• DNA Glycosylases
• oxoguanine glycosylase 1, human
• Glucose

Topics

• Animals
• DNA Glycosylases (metabolism)
• Glucose (toxicity)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Mice
• Models, Biological
• NADPH Oxidases (metabolism)
• Protein Kinase C (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)