1. GLP-1 treatment protects endothelial cells from oxidative stress-induced autophagy and endothelial dysfunction
- Author
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Xiangsheng Cai, Dianpeng Zheng, Shangliang Chen, She Miaoqin, Xu Xiaosong, Jingjing Li, Yang Xiaorong, Jianbin Zhu, Jinlong Li, Chen Shaolian, Huiying Chen, Xinglu Chen, Hongwei Li, Ruiying Li, Liu Jun, and Mingyu Xu
- Subjects
0301 basic medicine ,endocrine system ,autophagy ,Inflammation ,Oxidative phosphorylation ,medicine.disease_cause ,Histone Deacetylase 6 ,Applied Microbiology and Biotechnology ,endothelial dysfunction ,Glucagon-Like Peptide-1 Receptor ,03 medical and health sciences ,Downregulation and upregulation ,Glucagon-Like Peptide 1 ,Human Umbilical Vein Endothelial Cells ,Medicine ,Humans ,Endothelial dysfunction ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Membrane Potential, Mitochondrial ,business.industry ,Autophagy ,Endothelial Cells ,Cell Biology ,HDAC6 ,medicine.disease ,Peptide Fragments ,Oxidative Stress ,030104 developmental biology ,Cancer research ,Phosphorylation ,medicine.symptom ,business ,GLP-1 ,Reactive Oxygen Species ,Oxidative stress ,Developmental Biology ,Research Paper - Abstract
Endothelial dysfunction and excessively stimulated autophagy, often caused by oxidant injury or inflammation, will lead to atherosclerosis development and progression in diabetes. The aim of this study is to investigate the protective effect of glucagon-like peptide-1 (GLP-1) treatment on preventing oxidative stress-induced endothelial dysfunction and excessively stimulated autophagy. Treatment of endothelial cells with GLP-1 significantly attenuated oxidative stress-induced endothelial dysfunction and autophagy, which was associated with the reduction of intracellular reactive oxygen species (ROS) levels. These protective effects of GLP-1 were likely mediated by reducing phosphorylation of ERK1/2. We further demonstrated that GLP-1 treatment could reverse downregulation of epigenetic factor histone deacetylase 6 (HDAC6), a downstream molecular of the EKR1/2, induced by oxidant injury. In conclusion, our results suggest that GLP-1 produces a protective effect on endothelial cells from oxidant injury by preventing endothelial dysfunction and autophagy, which may be dependent on restoring HDAC6 through a GLP-1R-ERK1/2-dependent manner.
- Published
- 2018