Effects of annexin A1 mimic peptide Ac2-26 on ferroptosis and mitochondrial function of human umbilical vein endothelial cells induced by RSL3
10.20039/j.cnki.1007-3949.2025.04.004
- VernacularTitle:膜联蛋白A1模拟肽Ac2-26对RSL3诱导的人脐静脉内皮细胞铁死亡及线粒体功能的影响
- Author:
Shiming TAN
1
;
Zitong CAO
;
Jingjing WANG
;
Jinqiu JIA
;
Keyi LI
;
Zemin CAI
;
Zuo WANG
Author Information
1. 南华大学心血管疾病研究所动脉硬化学湖南省重点实验室湖南省动脉硬化性疾病国际科技创新合作基地
- Publication Type:Journal Article
- Keywords:
atherosclerosis;
ferroptosis;
mitochondria;
annexin A1;
Ac2-26;
RSL3
- From:
Chinese Journal of Arteriosclerosis
2025;33(4):303-309,341
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the effect and mechanism of annexin A1 mimic peptide Ac2-26 on ferroptosis in hu-man umbilical vein endothelial cells(HUVEC).Methods Induction of HUVEC ferroptosis was achieved by the clas-sical ferroptosis agonist RSL3,with subsequent intervention by the annexin A1 mimtic peptide Ac2-26.The cell number and viability were detected by CCK-8 kit,the levels of malondialdehyde(MDA)and glutathione(GSH)were detected by ELISA,the expression of ferroptosis-related molecules and adhesion molecules was detected by Western blot,the lipid re-active oxygen species(ROS)levels were detected by C11-BODIPY fluorescent probe,and the mitochondrial reactive oxy-gen species(mtROS)levels were detected by MitoSOX probe.FeRhoNOX-1 fluorescent probe was used to detect intra-cellular Fe2+content,perspective microscopy was used to observe mitochondrial morphology,JC-1 fluorescent probe was used to detect mitochondrial membrane potential,kit was used to detect ATP levels,the Scratch assay was used to detect cell migration ability,and nitrate reductase assay was used to detect nitric oxide(NO)level.Results Ac2-26 inhibi-ted RSL3-induced decrease in HUVEC viability,up-regulated the expression of suppressor of ferroptosis proteolytic carrier family 7 member 11(SLC7A11),GPX4,and ferritin heavy chain 1(FTH1),increased the GSH content,decreased the MDA content,reduced the generation of intracellular lipid ROS,and decreased the intracellular Fe2+aggregation(P＜0.05 or P＜0.01);Ac2-26 inhibited RSL3-induced damage to HUVEC mitochondrial morphology and function,up-regulated ATP content(P＜0.05)and mitochondrial membrane potential(P＜0.001);Ac2-26 inhibited RSL3-induced decrease in HUVEC migratory ability,up-regulated NO levels,inhibited intercellular adhesion molecule-1(ICAM-1)and interleukin-1β(IL-1β)protein expression(P＜0.05 or P＜0.01).Conclusion Ac2-26 inhibits RSL3-induced ferroptosis in HUVEC and maintains mitochondrial morphology and function,as well as HUVEC function.
