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p53 Promotes Ferroptosis in Macrophages Treated with Fe 3 O 4 Nanoparticles.
- Source :
-
ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2022 Sep 28; Vol. 14 (38), pp. 42791-42803. Date of Electronic Publication: 2022 Sep 16. - Publication Year :
- 2022
-
Abstract
- Fe <subscript>3</subscript> O <subscript>4</subscript> nanoparticles are the most widely used magnetic nanoparticles in the biomedicine field. The biodistribution of most nanoparticles in vivo is determined by the capture of macrophages; however, the effects of nanoparticles on macrophages remain poorly understood. Here, we demonstrated that Fe <subscript>3</subscript> O <subscript>4</subscript> nanoparticles could reduce macrophage viability after 48 h of treatment and induce a shift in macrophage polarization toward the M1 phenotype; RNA sequencing revealed the activation of the ferroptosis pathway and p53 upregulation compared to the control group. The expression in p53, xCT, glutathione peroxidase 4 (GPX4), and transferrin receptor (TFR) in macrophages was similar to that in erastin-induced ferroptosis in macrophages, and the ultrastructural morphology of mitochondria was consistent with that of erastin-treated cells. We used DCFH-DA to estimate the intracellular reactive oxygen species content in Fe <subscript>3</subscript> O <subscript>4</subscript> nanoparticles treated with Ana-1 and JC-1 fluorescent probes to detect the mitochondrial membrane potential change; both showed to be time-dependent. Fer-1 inhibited the reduction of the glutathione/oxidized glutathione (GSH/GSSG) ratio and inhibited intracellular oxidative stress states; therefore, Fe <subscript>3</subscript> O <subscript>4</subscript> nanoparticles induced ferroptosis in macrophages. Finally, we used pifithrin-α hydrobromide (PFT) as a p53 inhibitor to verify whether the high expression of p53 is involved in mediating this process. After PFT treatment, the live/dead cell rate, TFR, p53 expression, and GPX4 consumption were inhibited and mitigated the GSH/GSSG ratio reduction as well. This indicates that p53 may contribute to Fe <subscript>3</subscript> O <subscript>4</subscript> nanoparticle-induced ferroptosis of macrophages. We provide a theoretical basis for the molecular mechanisms of ferroptosis in macrophages and the biotoxicity in vivo induced by Fe <subscript>3</subscript> O <subscript>4</subscript> nanoparticles.
- Subjects :
- Fluorescent Dyes
Glutathione metabolism
Glutathione Disulfide metabolism
Macrophages metabolism
Phospholipid Hydroperoxide Glutathione Peroxidase
Reactive Oxygen Species metabolism
Receptors, Transferrin metabolism
Tissue Distribution
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Protein p53 metabolism
Ferroptosis
Nanoparticles
Subjects
Details
- Language :
- English
- ISSN :
- 1944-8252
- Volume :
- 14
- Issue :
- 38
- Database :
- MEDLINE
- Journal :
- ACS applied materials & interfaces
- Publication Type :
- Academic Journal
- Accession number :
- 36112832
- Full Text :
- https://doi.org/10.1021/acsami.2c00707