Xiangrong Xie1, Yan Chen2, Jichun Liu1, Wenbo Zhang1, Xuan Zhang1, Lintao Zha1, Wenjie Liu1, Yang Ling1, Shu Li3, Shengxing Tang4. 1. Department of Cardiology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, PR China. 2. Department of Cardiology, Taishan People's Hospital, Taishan, Guangdong 529200, PR China. 3. Department of Pathophysiology, Wannan Medical College, Wuhu, Anhui 241002, PR China. Electronic address: wylishu@wnmc.edu.cn. 4. Department of Cardiology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, PR China. Electronic address: tsx2229@163.com.
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.
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.