Investigation of Effects And Mechanisms of Nrf2-ARE Pathway on Uremic Serum-Mediated Endothelial Dysfunction in Human Aortic Endothelial Cells
- VernacularTitle:激活Nrf2-ARE通路改善尿毒症患者血清诱导的内皮细胞功能障碍及其机制
- Author:
Wenjie DENG
;
Qunzi ZHANG
;
Qiongxia DENG
;
Hui PENG
;
Cheng WANG
;
Tanqi LOU
- Keywords:
uremic serum;
endothelial dysfunction;
oxidative stress;
endothelial nitric oxide synthase (eNOS);
nuclear factor erythroid-2 related factor-antioxidant response element (Nrf2-ARE);
tert-Butylhydroquinone (tBHQ)
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2017;38(3):341-349
- CountryChina
- Language:Chinese
-
Abstract:
[Objective] To investigate the effects and mechanisms of Nrf2-ARE (nuclear factor erythroid-2 related factor-anti-oxidant response element) pathway on uremic serum-mediated endothelial dysfunction in human aortic endothelial ceils.[Methods] Human aortic endothelial cells were incubated in endothelial cell medium containing 10％ normal serum,10％ non-diabetic nuremic serum or 10％ diabetic uremic serum respectively,and 20 μmol/L tertiary butyl hydroquinone (tBHQ) were pretreated with cells to active Nrf2-ARE pathway.The cells apoptosis rate were measured by flow cytometry,and the synthesis of NO was detected by flow cytometry and immune fluorescent confocal,while the expression of P-eNOSer1177/eNOS,and quinone oxidoreductase-1 (NQO1) were measured by western blotting.The levels of malondialdehyde,superoxide dismutase,eatalase,and glutathione in these cells were also measured with kits.[Results] Aortic endothelial cells incubated with uremic serum had a higher level of apoptosis rate and MDA (P ＜ 0.05),and a lower level of NO systhesis,P-eNOSSer1177/eNOS expression,CAT,SOD,GSH (P ＜ 0.05).Pretreated with tBHQ can reduce the apoptosis rate and MDA level (P ＜ 0.05),improve the amount of NO systhesis,the expression of P-eNOSSer1177/eNOS,the levels of CAT,SOD,and GSH in these cells (P ＜ 0.05).[Conclusion] Activation of Nrf2-ARE pathway can improve endothelial dysfunction in aortic endothelial cells induced by uremic serum,and its mechanism might be related with enhancement of the antioxidant stress.
