MAPK signaling mediates low shear stress-induced oxidative damage in human umbilical vein endothelial cells in vitro
10.3969/j.issn.1673-4254.2014.05.02
- VernacularTitle:MAPK信号通路介导低剪切力诱导的人脐静脉内皮细胞氧化应激性损伤
- Author:
Zhimei WANG
1
;
Junxia ZHANG
;
Bing LI
;
Wenxing MAO
;
Shaoliang CHEN
Author Information
1. 南京医科大学附属南京医院心内科
- Keywords:
shear stress;
endothelial cells;
atherosclerosis;
MAPK signaling pathway;
oxidative stress
- From:
Journal of Southern Medical University
2014;(5):603-608
- CountryChina
- Language:Chinese
-
Abstract:
Objective Atherosclerotic lesions occur preferentially in the arterial branches, bifurcations and curvatures where shear stress is low. We aimed to study the possible mechanisms involved in low shear stress (LSS)-induced oxidative damage in vascular endothelial cells. Methods Human umbilical vein endothelial cells (HUVECs) exposed for 60 min to simulated LSS using a parallel-plate flow chamber were examined for intracellular reactive oxygen species (ROS) and cell apoptosis with chemiluminescence assay and TUNEL staining, respectively. Western blotting was used to determine the levels of endothelial nitric oxide synthase (eNOS), P38, extracellular signal-regulate kinase (ERK) and c-Jun as well as their phosphorylation in cells with LSS exposure for different time lengths. To investigate the signaling pathway involved in LSS-induced oxidative damage, the cells were treated with P38, ERK and c-Jun inhibitors and examined for the expression of eNOS-Thr495 that negatively regulated eNOS. Results Exposure to LSS for 1 h resulted in markedly increased ROS accumulation and apoptosis in HUVECs. LSS exposure time-dependently enhanced the phosphorylation of eNOS, P38, ERK and c-Jun but did not significantly affect their total protein expressions. Inhibition of ERK with PD98059 deactivated eNOS-Thr495 and restored super oxide dismutase (SOD) activity, while inhibition of either p38 with SB202190 or c-Jun with SP600125 did no produce such effects. Conclusion LSS-induced oxidative damage is partly due to activated mitogen-activated protein kinases (MAPK), among which ERK contributes to decreased NO release in endothelial cells.
