N-myc downstream-regulated gene 1 aggravates ferroptosis in brain microvascular endothelial cells induced by oxygen-glucose deprivation
10.3969/j.issn.1009-0126.2025.06.023
- VernacularTitle:N-myc下游调控基因1加重氧糖剥夺脑微血管内皮细胞铁死亡的作用研究
- Author:
Haifeng HUANG
1
;
Yuyuan GAO
1
;
Qingrui DUAN
1
;
Lijuan WANG
1
Author Information
1. 510080 广州,南方医科大学附属广东省人民医院(广东省医学科学院)神经科
- Publication Type:Journal Article
- Keywords:
stroke;
ferroptosis;
endothelial cells;
hypoxia-ischemia,brain;
genes,myc
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2025;27(6):798-803
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of N-myc downstream regulated gene 1(NDRG1)on ferroptosis in mouse brain microvascular endothelial cells(BMVEC)induced by oxygen-glu-cose deprivation(OGD).Methods After primary BMVEC were isolated and cultured from mice,electron microscopy was used to observe the mitochondrial morphology of the cells after OGD.bEnd.3 cells were cultured and divided into six groups:control group,model group(OGD),si-NC(negative control)group,si-NDRG1(NDRG1 interference RNA)group,OGD+si-NC(negative control modeling)group,and OGD+si-NDRG1(NDRG1 interference)group(n=3).The model group,OGD+si-NC group,and OGD+si-NDRG1 group were subjected to the OGD model.Si-NC transfection was performed in the si-NC and OGD+si-NC groups,while si-NDRG1 transfection was carried out in the si-NDRG1 and OGD+si-NDRG1 groups.Cell viability,MDA,glutathione,Fe2+,lipid peroxidation levels,and protein levels of NDRG1,glutathione peroxidase 4(GPX4),and acyl-CoA synthetase long-chain family member 4(ACSL4)were detected in each group.Results Compared with the control group,the model group showed a significant reduction in the number of cells adhering to the surface after OGD treatment,swollen cytoplasm and decrease in cell viability[(37.68±2.43)％vs(96.34±12.08)％,P＜0.05],down-regulation of GPX4 and up-regulation of ACSL4 and NDRG1 expression(0.78±0.02 vs 1.15±0.01,P＜0.01;1.45±0.04 vs 0.78±0.12,P＜0.01;1.22±0.01 vs 0.13±0.01,P＜0.01).In the si-NDRG1 group,the protein levels of GPX4 and NDRG1 were significantly lower,while the protein levels of ACSL4 and gluta-thione were significantly higher than the si-NC group(P＜0.05).The OGD+si-NC group showed significantly lower GPX4 expression and glutathione level,while obviously higher NDRG1,ACSL4 expression,MDA,and relative fluorescence intensities of Fe2+and oxidized lipid levels when compared to the si-NC and si-NDRG1 groups(P＜0.05).The OGD+si-NDRG1 group showed significantly lower GPX4 expression and glutathione level,and higher ACSL4 and relative fluorescence intensity of Fe2+than the si-NC group and the si-NDRG1 group,while lower NDRG1 expression than the si-NC group but higher than the si-NDRG1 group,and lower NDRG1,ACSL4,MDA,and relative fluorescence intensities of Fe2+and oxidized lipids when compared with the OGD+si-NC group(P＜0.05).Conclusion Knockdown of NDRG1 can alleviate OGD-induced ferroptosis in microvascular endothelial cells by improving iron metabolism and lipid per-oxidation.
