Ferrostatin-1 improves BMSC survival by inhibiting ferroptosis.
Arch Biochem Biophys
; 736: 109535, 2023 03 01.
Article
em En
| MEDLINE
| ID: mdl-36708941
ABSTRACT
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 potential, 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases Ativadas por AMP
/
Ferroptose
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article