scholarly journals Down-Regulation of MicroRNA-137 Improves High Glucose-Induced Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells by Up-Regulation of AMPKα1

2016 ◽  
Vol 39 (3) ◽  
pp. 847-859 ◽  
Author(s):  
Jie Li ◽  
Junfeng Li ◽  
Tingting Wei ◽  
Junhua Li

Background/Aims: To investigate the effects of miR-137 on high glucose (HG)-induced vascular injury, and to establish the mechanism underlying these effects. Methods: Human umbilical vein endothelial cells (HUVECs) were transfected with miR-137 inhibitor or mimic, and then treated with normal or high glucose. Cell viability and apoptosis were detected by using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by fluorescent probe (DCFH-DA), thiobarbituric acid reaction, and the nitroblue tetrazolium assay, respectively. The mRNA and protein expressions of AMPKα1 were determined by qRT-PCR and Western blotting. Results: Down-regulation of miR-137 dramatically reverted HG-induced decreases in cell viability and SOD levels and increases in apoptosis, ROS and MDA levels. Moreover, bioinformatics analysis predicted that the AMPKα1 was a potential target gene of miR-137. Luciferase reporter assay demonstrated that miR-137 could directly target AMPKα1. AMPKα1 overexpression had the similar effect as miR-137 inhibition. Down-regulation of AMPKα1 in HUVECs transfected with miR-137 inhibitor partially reversed the protective effect of miR-137 inhibition on HG-induced oxidative stress in HUVECs. Conclusion: Down-regulation of miR-137 ameliorates HG-induced injury in HUVECs by overexpression of AMPKα1, leading to increasing cellular reductive reactions and decreasing oxidative stress. These results provide further evidence for protective effect of miR-137 inhibition on HG-induced vascular injury.

2016 ◽  
Vol 71 (1-2) ◽  
pp. 21-28 ◽  
Author(s):  
Mi Hwa Park ◽  
Jae-Won Ju ◽  
Mihyang Kim ◽  
Ji-Sook Han

AbstractEndothelial cell dysfunction is considered a major cause of vascular complications in diabetes. In the present study, we investigated the protective effect of daidzein, a natural isoflavonoid, against high-glucose–induced oxidative damage in human umbilical vein endothelial cells (HUVECs). Treatment with a high concentration of glucose (30 mM) induced oxidative stress in the endothelial cells, against which daidzein protected the cells as demonstrated by significantly increased cell viability. In addition, lipid peroxidation, intracellular reactive oxygen species (ROS) generation, and indirect nitric oxide levels induced by the high glucose treatment were significantly reduced in the presence of daidzein (0.02–0.1 mM) in a dose-dependent manner. High glucose levels induced the overexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB proteins in HUVECs, which was suppressed by treatment with 0.04 mM daidzein. These findings indicate the potential of daidzein to reduce high glucose-induced oxidative stress.


2017 ◽  
Vol 45 (06) ◽  
pp. 1201-1216 ◽  
Author(s):  
Li-Yen Huang ◽  
I-Chuan Yen ◽  
Wei-Cheng Tsai ◽  
Blerina Ahmetaj-Shala ◽  
Tsu-Chung Chang ◽  
...  

Rhodiola crenulata root extract (RCE), a traditional Chinese medicine, has been shown to regulate glucose and lipid metabolism via the AMPK pathway in high glucose (HG) conditions. However, the effect of RCE on HG-induced endothelial dysfunction remains unclear. The present study was designed to examine the effects and mechanisms of RCE against hyperglycemic insult in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were pretreated with or without RCE and then exposed to 33[Formula: see text]mM HG medium. The cell viability, nitrite production, oxidative stress markers, and vasoactive factors, as well as the mechanisms underlying RCE action, were then investigated. We found that RCE significantly improved cell death, nitric oxide (NO) defects, and oxidative stress in HG conditions. In addition, RCE significantly decreased the HG-induced vasoactive markers, including endothelin-1 (ET-1), fibronectin, and vascular endothelial growth factor (VEGF). However, the RCE-restored AMPK-Akt-eNOS-NO axis and cell viability were abolished by the presence of an AMPK inhibitor. These findings suggested that the protective effects of RCE were associated with the AMPK-Akt-eNOS-NO signaling pathway. In conclusion, we showed that RCE protected endothelial cells from hyperglycemic insult and demonstrated its potential for use as a treatment for endothelial dysfunction in diabetes mellitus.


2007 ◽  
Vol 566 (1-3) ◽  
pp. 1-10 ◽  
Author(s):  
Hiroshi Tsuneki ◽  
Naoto Sekizaki ◽  
Takashi Suzuki ◽  
Shinjiro Kobayashi ◽  
Tsutomu Wada ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jingshang Wang ◽  
Huijun Yin ◽  
Ye Huang ◽  
Chunyu Guo ◽  
Chengdong Xia ◽  
...  

Panax quinquefolius saponin of stem and leaf (PQS), the effective parts of American ginseng, is widely used in China as a folk medicine for diabetes and cardiovascular diseases treatment. In our previous studies, we have demonstrated that PQS could improve the endothelial function of type II diabetes mellitus (T2DM) rats with high glucose fluctuation. In the present study, we investigated the protective effects of PQS against intermittent high glucose-induced oxidative damage on human umbilical vein endothelial cells (HUVECs) and the role of phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3βpathway involved. Our results suggested that exposure of HUVECs to a high glucose concentration for 8 days showed a great decrease in cell viability accompanied by marked MDA content increase and SOD activity decrease. Moreover, high glucose significantly reduced the phosphorylation of Akt and GSK-3β. More importantly, these effects were even more evident in intermittent high glucose condition. PQS treatment significantly attenuated intermittent high glucose-induced oxidative damage on HUVECs and meanwhile increased cell viability and phosphorylation of Akt and GSK-3βof HUVECs. Interestingly, all these reverse effects of PQS on intermittent high glucose-cultured HUVECs were inhibited by PI3K inhibitor LY294002. These findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative stress injury in HUVECs by PI3K/Akt/GSK-3βpathway.


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