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Updated: Jul 5, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Methionine enkephalin (MENK) protected macrophages from ferroptosis by downregulating HMOX1 and ferritin
Jing Tian1, Wenrui Fu2, Zifeng Xie3
1Department of Immunology, School of Basic Medical Science, Jinzhou Medical University, Jinzhou, Liaoning, 121000, China. tianjing@jzmu.edu.cn.
Objective:
The aim of this work was to investigate the immunological effect of MENK by analyzing the protein spectrum and bioinformatics of macrophage RAW264.7, and to explore the relationship between macrophage and ferroptosis.
Result:
We employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages and macrophages intervened by MENK. A total of 208 DEPs were identified. Among these, 96 proteins had upregulated expression and 112 proteins had downregulated expression. Proteomic analysis revealed a significant enrichment of DEPs associated with iron metabolism. The identification of hub genes was conducted using KEGG pathway diagrams and protein-protein interaction (PPI) analysis. The hub genes identified in this study include HMOX1 and Ferritin (FTH and FTL). A correlation was established between HMOX1, FTH, and FTL in the GO and KEGG databases. The results of PCR, WB and immunofluorescence showed that MENK downregulated the level of HMOX1 and FTH.
Conclusion:
MENK had the potential to become an adjuvant chemotherapy drug by regulating iron metabolism in macrophages, reducing levels of HMOX1 and ferritin. We proposed an innovative research direction on the therapeutic potential of MENK, focusing on the relationship between ferroptosis and macrophage activity.
Insights
MENK regulates macrophage iron metabolism by downregulating HMOX1 and ferritin, suggesting its potential as an adjuvant chemotherapy drug. This study explores the link between macrophage activity and ferroptosis.
Area of Science:
- Immunology
- Biochemistry
- Bioinformatics
Background:
- Macrophages play a crucial role in immune responses.
- Ferroptosis, an iron-dependent form of cell death, is implicated in various diseases.
- Understanding the interplay between macrophages and ferroptosis is vital for therapeutic development.
Purpose of the Study:
- To investigate the immunological effects of MENK on macrophage RAW264.7 cells.
- To analyze the protein spectrum and conduct bioinformatics analysis of MENK-treated macrophages.
- To explore the relationship between macrophage function and ferroptosis.
Main Methods:
- Proteomic analysis to identify differentially expressed proteins (DEPs) in MENK-treated macrophages.
- Bioinformatic analyses including KEGG pathway and protein-protein interaction (PPI) analysis to identify hub genes.
- Validation of key gene expression using PCR, Western blot (WB), and immunofluorescence.
Main Results:
- Identified 208 DEPs, with 96 upregulated and 112 downregulated.
- Significant enrichment of DEPs related to iron metabolism.
- Identified HMOX1, FTH, and FTL as hub genes, with MENK downregulating HMOX1 and FTH levels.
Conclusions:
- MENK modulates macrophage iron metabolism by reducing HMOX1 and ferritin levels.
- MENK shows potential as an adjuvant chemotherapy agent.
- Proposed a novel research direction focusing on MENK's therapeutic potential in ferroptosis and macrophage activity.

