NADPH oxidase-dependent heme oxygenase-1 expression mediates cigarette smoke-induced ferroptosis via intracellular Fe(II) accumulation
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View abstract on PubMed
Summary
This summary is machine-generated.Cigarette smoke induces ferroptosis, a cell death pathway, in chronic obstructive pulmonary disease (COPD). Heme oxygenase-1 (HO-1) is a key mediator, suggesting it as a therapeutic target for COPD.
Area Of Science
- Cell Biology
- Pulmonary Medicine
- Toxicology
Background
- Ferroptosis, a form of programmed cell death, is linked to chronic obstructive pulmonary disease (COPD) pathogenesis.
- The exact role and contributing factors of ferroptosis in COPD remain unclear.
Purpose Of The Study
- To investigate the relationship between ferroptosis and COPD.
- To elucidate the underlying mechanisms of ferroptosis in COPD, focusing on key mediators.
Main Methods
- Utilized human bronchial epithelial cells (BEAS-2B) treated with cigarette smoke extract (CSE) and ferroptosis inhibitors.
- Assessed cell viability, lipid peroxidation markers (MDA, 4-HNE), iron levels, and ferroptosis-related proteins (GPX4, HO-1).
- Validated findings in a CSE-induced COPD mouse model.
Main Results
- CSE induced ferroptosis in BEAS-2B cells and mouse lungs, characterized by increased lipid peroxidation, iron, and HO-1, with decreased GPX4.
- CSE-induced cell death and ferroptosis were ameliorated by ferroptosis inhibitors (Fer-1, DFO, NAC).
- Heme oxygenase-1 (HO-1) was identified as a crucial mediator, with its modulation affecting CSE-induced cell death.
Conclusions
- Cigarette smoke-induced ferroptosis is a significant contributor to COPD development.
- Heme oxygenase-1 (HO-1) plays a critical role in mediating CS-induced ferroptosis in COPD.
- HO-1 represents a potential therapeutic target for managing COPD.
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