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[FER-1 inhibits methylglyoxal-induced ferroptosis in mouse alveolar macrophages in vitro]
Qi Zhang1, Zezhao Ji1, Abai Jiashaer1
1Department of Histology and Embryology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830000, China.
Objectives:
To investigate the inhibitory effect of FER-1 on methylglyoxal-induced ferroptosis in cultured mouse alveolar macrophages.
Methods:
MH-S cells derived from mouse alveolar macrophages treated with 90 μg/mL methylglyoxal, 10 μmol/mL FER-1MG+FER-1, or both were examined for intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and ferrous ion (Fe2+) levels and changes in mitochondrial membrane potential. Western blotting was performed to detect the protein expression levels of glutathione peroxidase 4 (GPX4) and long-chain acyl-CoA synthase 4 (ACSL4).
Results:
Methylglyoxal treatment of MH-S cells for 24 h significantly decreased the protein expression level of GPX4, upregulated the protein expression of ACSL4, increased intracellular concentrations of ferrous ions, ROS and MDA, caused loss of mitochondrial membrane potential, and decreased cell viability. Treatment of the cells with FER-1 effectively attenuated these detrimental effects of methylglyoxal in MH-S cells by increasing GPX4 expression, reducing ACSL4 expression and intracellular ferrous ions, ROS and MDA levels, and restoring the mitochondrial membrane potential.
Conclusions:
Methylglyoxal can induce ferroptosis in MH-S cells in a dose-dependent manner, and FER-1 can rescue the cells from methylglyoxal-induced ferroptosis.
Insights
FER-1 inhibits methylglyoxal-induced ferroptosis in mouse alveolar macrophages. This compound protects cells by reducing oxidative stress and restoring mitochondrial function, offering a potential therapeutic strategy.
Area of Science:
- Cellular Biology
- Biochemistry
- Toxicology
Context:
- Methylglyoxal is a reactive dicarbonyl compound implicated in cellular damage.
- Ferroptosis is a regulated form of cell death characterized by iron accumulation and lipid peroxidation.
- Alveolar macrophages play a crucial role in lung immunity and are susceptible to oxidative stress.
Purpose:
- To investigate the protective effects of FER-1 against methylglyoxal-induced ferroptosis.
- To elucidate the underlying molecular mechanisms of FER-1's action in macrophages.
Summary:
- Methylglyoxal treatment induced ferroptosis in MH-S cells, evidenced by decreased GPX4, increased ACSL4, elevated ROS, MDA, and ferrous ions, and mitochondrial dysfunction.
- FER-1 treatment attenuated these effects, restoring GPX4 levels, reducing ACSL4, and mitigating oxidative stress and mitochondrial damage.
- These findings demonstrate FER-1's efficacy in preventing methylglyoxal-induced ferroptosis in a dose-dependent manner.
Impact:
- Provides evidence for FER-1 as a potential therapeutic agent against methylglyoxal-induced cellular damage.
- Highlights the role of ferroptosis in methylglyoxal toxicity.
- Offers insights into the modulation of ferroptosis pathways in lung macrophages.
