Ferrostatin-1 improves BMSC survival by inhibiting ferroptosis

作者全名："Xie, Qiumin; Sun, Yanting; Xu, Hao; Chen, Tangtian; Xiang, Han; Liu, Huiwen; Wang, Rui; Tan, Bin; Yi, Qin; Tian, Jie; Zhu, Jing"

作者地址："[Xie, Qiumin; Sun, Yanting; Chen, Tangtian; Xiang, Han; Liu, Huiwen; Wang, Rui; Tan, Bin; Yi, Qin; Zhu, Jing] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders,Dept Ped, Chongqing 400014, Peoples R China; [Xu, Hao] Chongqing Med Univ, Dept Clin Lab, Childrens Hosp, Chongqing 400014, Peoples R China; [Tian, Jie] Chongqing Med Univ, Dept Cardiovasc Internal Med, Childrens Hosp, Chongqing 400014, Peoples R China"

通信作者："Zhu, J (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders,Dept Ped, Chongqing 400014, Peoples R China."

来源：ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000933066800001

JCR分区：Q1

影响因子：3.8

年份：2023

卷号：736

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：BMSCs; GSDH; Ferroptosis; Ferrostatin-1; AMPK

摘要："Objective: To investigate the effect of ferroptosis in BMSCs and explore the protective metabolism of ferrostatin-1 under GSDH treatment.Methods: BMSCs were treated with GSDH to simulate the damaged microenvironment in vivo to establish a cell injury model. Propidium iodide and CCK8 were utilized to detect the ratio of dead cells and cell viability. DCFH-DA and Amplex Red, FerroOrange, and BPDIPY were used to visualize the cellular fluorescent images of ROS, Fe2+, and lipid droplets, respectively. The quantified detection of MDA was conducted by a Lipid Peroxidation MDA Assay Kit. JC-1 staining, Mito-Tracker staining, and TEM were implemented to detect the membrane po-tential, morphology, and ultrastructure of mitochondria, respectively. The expression levels of ferroptosis-related proteins such as GPX4 and FTH1 were measured by Western blotting.Results: GSDH treatment induced ferroptosis in BMSCs based on an increased ratio of cell death, Fe2+, ROS, lipid droplets, and MDA in cells plus decreased protein levels of antioxidant systems, such as GPX4, and increased protein levels related to fatty acid synthesis. Compared to the blank group, mitochondria in the GSDH group underwent lower membrane potential, damaged morphology, and shrunken ultrastructure; Ferr-1 rescued the injured BMSCs to a certain extent as the declined ratio of cell death, Fe2+, ROS, lipid droplets, MDA, and the increased level antioxidant protein. AMPK was phosphorylated and activated after Ferr-1 treatment, and its downstream lipid peroxidation and antioxidation proteins changed accordingly. Inhibition of AMPK hindered the curative effect of Ferr-1.Conclusion: Ferr-1 rescued ferroptosis-induced injury to BMSCs under GSDH conditions, and AMPK might have a relationship with the mitigative effect of Ferr-1."

基金机构：National Natural Science Foundation of China [81970244]

基金资助正文：This work was supported by the National Natural Science Foundation of China (81970244) .