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.

Proteome Science
|January 20, 2024
PubMed
Abstract

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.