The dual role of FSP1 in programmed cell death: resisting ferroptosis in the cell membrane and promoting necroptosis in the nucleus of THP-1 cells.
AML-M5
FSP1
Ferroptosis
Myristoylation
Necroptosis
THP-1 cells
Journal
Molecular medicine (Cambridge, Mass.)
ISSN: 1528-3658
Titre abrégé: Mol Med
Pays: England
ID NLM: 9501023
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
02
02
2024
accepted:
10
06
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
15
7
2024
Statut:
epublish
Résumé
Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear. THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot. The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis. We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.
Sections du résumé
BACKGROUND
BACKGROUND
Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear.
METHODS
METHODS
THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot.
RESULTS
RESULTS
The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis.
CONCLUSION
CONCLUSIONS
We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.
Identifiants
pubmed: 39009982
doi: 10.1186/s10020-024-00861-4
pii: 10.1186/s10020-024-00861-4
doi:
Substances chimiques
Reactive Oxygen Species
0
AGFG1 protein, human
0
N-(4-(N-(3-methoxypyrazin-2-yl)sulfamoyl)phenyl)-3-(5-nitrothiophene-2-yl)acrylamide
0
Piperazines
0
erastin
0
Acrylamides
0
Sulfonamides
0
RNA-Binding Proteins
0
Nuclear Pore Complex Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102Subventions
Organisme : the National Natural Sciences Foundation of China
ID : 81800386
Organisme : the Hunan Provincial Natural Science Foundation of China
ID : 2021JJ30020
Organisme : the financial supports from the scientific research project of health commission of Hunan province
ID : 202101021784
Organisme : the financial supports from the science and technology plan project of Hengyang City
ID : 202150063459
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : 202110555098
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : S202110555307
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : X202110555516
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : X202110555523
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : X202110555529
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : S202210555256
Organisme : College Students' Research Learning and Innovative Experiment Plan in University of South China
ID : 2022X10555115
Informations de copyright
© 2024. The Author(s).
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