Department of Cardiology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui 241001, PR China.
Department of Cardiology, Taishan People's Hospital, Taishan, Guangdong 529200, PR China.
Life Sci. 2020 Sep 1;256:117886. doi: 10.1016/j.lfs.2020.117886. Epub 2020 Jun 1.
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.
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.
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.
These results suggest that OGG1 downregulation promoted HG-induced endothelial ROS production and might be a potential clinical treatment target of diabetics.
高葡萄糖（HG）引起的活性氧（ROS）涉及许多疾病，包括糖尿病。然而，HG 诱导 ROS 的潜在机制仍不清楚。新出现的证据表明，8-氧鸟嘌呤糖苷酶（OGG1）是负责动脉粥样硬化、肥胖、肝脂肪变性和胰岛素抵抗等疾病的主要 DNA 糖苷酶。我们的目的是探讨 OGG1 在 HG 介导的内皮 ROS 中的作用。
用人脐静脉内皮细胞（HUVEC）暴露于不同时间的 HG（30mM）。Western blot、qPCR 和免疫荧光法测量表明，HG 以时间依赖性方式显著抑制 OGG1 的表达。此外，HUVEC 在用 HG 处理后用荧光探针 DCFH 和 DHE 培养。细胞化学发光和流式细胞术结果表明，HG 引起内皮细胞 ROS 激活。
高葡萄糖显著降低内皮 OGG1 的表达。OGG1 的过表达显著逆转了 HG 介导的 PKC 和 NADPH 氧化酶活性和 ROS 水平。此外，PKC 的操纵表达显著影响了 OGG1 对 NADPH 氧化酶激活的作用。
这些结果表明，OGG1 的下调促进了 HG 诱导的内皮细胞 ROS 产生，可能成为糖尿病患者的潜在临床治疗靶点。
