Mitochondrial damage induced by iron overload viaeNOS in vascular endothelial cells
10.3969/j.issn.1001-1978.2017.10.025
- VernacularTitle:eNOS参与铁过载诱导的血管内皮细胞线粒体损伤
- Author:
Huan HE
;
Zeyu ZHANG
;
Dan LIU
;
Zhangping LIAO
;
Dong YIN
;
Ming HE
- Keywords:
iron overload;
mitochondria;
ADMA;
eNOS;
DDAH II;
cell apoptosis
- From:
Chinese Pharmacological Bulletin
2017;33(10):1457-1461
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the damage of mitochondria in HUVECs cells by iron overload and the role of ADMA/eNOS/DDAHⅡ in it.Methods HUVECs cells were cultured and randomly divided into normal control (Ctrl) group, dextran iron (Iron) group and L-arginine (L-Arg) group.After 48 h, the survival rate of cells was detected by MTT assay;ADMA content and DDAHⅡactivity were measured by HPLC method;the expression of eNOS was determined by Western blot;LDH activity, MDA and NO content, and mitochondrial permeability transition pores(mPTP) openness were determined by colorimetric assay;ROS generation, mitochondrial membrane potential and apoptosis were determined by flow cytometry.Results After 48 h treatment with iron, the survival rate of HUVECs significantly decreased, while the activity of LDH in culture medium increased.The results showed that ADMA and MDA content significantly increased, NO content, DDAHⅡactivity, and the expression of eNOS markedly decreased, the generation of ROS was evidently elevated, mitochondrial membrane potential was lost apparently, mPTP openness was obvious, and the apoptosis of the HUVECs were worsened.However, as ADMA physiological antagonist, L-Arg significantly attenuated the above effects of iron.Conclusion Iron overload could damage mitochondrial function by eNOS and induce the apoptosis of HUVECs, in which ADMA/DDAHⅡ mechanism may also be engaged.
