2025年6月23日 周一
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Effects of annexin A1 mimic peptide Ac2-26 on ferroptosis and mitochondrial function of human umbilical vein endothelial cells induced by RSL3
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1.Institute of Cardiovascular Disease, University of South China & Key Laboratory of Arterial Hard Chemistry of Hunan Province & Hunan Province Arteriosclerotic Disease International Scientific and Technological Innovation Cooperation Base, Hengyang, Hunan 421001, China;2.The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China)

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R5;R363

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    Abstract:

    Aim To explore the effect and mechanism of annexin A1 mimic peptide Ac2-26 on ferroptosis in human umbilical vein endothelial cells (HUVEC). Methods Induction of HUVEC ferroptosis was achieved by the classical 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 reactive oxygen species (ROS) levels were detected by C11-BODIPY fluorescent probe, and the mitochondrial reactive oxygen species (mtROS) levels were detected by MitoSOX probe. FeRhoNOX-1 fluorescent probe was used to detect intracellular 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 inhibited 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.

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TAN Shiming, CAO Zitong, WANG Jingjing, JIA Jinqiu, LI Keyi, CAI Zemin, WANG Zuo. Effects of annexin A1 mimic peptide Ac2-26 on ferroptosis and mitochondrial function of human umbilical vein endothelial cells induced by RSL3[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2025,33(4):303-309, 341.

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History
  • Received:October 25,2024
  • Revised:March 18,2025
  • Online: May 16,2025
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