Endogenous oxidized phospholipid POVPC triggers pulmonary epithelial ferroptosis in acute lung injury and is restrained by RCN3 - PubMed
3 hours ago
- #oxidized phospholipid
- #acute lung injury
- #ferroptosis
- Endogenous oxidized phospholipid POVPC triggers pulmonary epithelial ferroptosis in acute lung injury (ALI).
- RCN3 acts as a protective intracellular safeguard against POVPC-induced ferroptosis.
- POVPC levels are significantly increased in LPS-induced ALI lungs.
- POVPC exposure induces ferroptosis in pulmonary epithelial cells, characterized by iron accumulation, lipid peroxidation, and depletion of GSH, GPX4, and SLC7A11.
- Ferroptosis caused by POVPC can be reversed by ferrostatin-1 and deferoxamine.
- POVPC initially upregulates RCN3, but sustained exposure leads to RCN3 exhaustion and worsened ferroptosis.
- RCN3 knockdown aggravates POVPC-induced ferroptosis, while overexpression attenuates it.
- AECII-specific RCN3 deletion sensitizes mice to POVPC-induced ALI, whereas AAV6-RCN3 delivery alleviates lung injury and ferroptosis.
- POVPC is identified as an endogenous contributor to epithelial ferroptosis in ALI, with RCN3 serving as a stress-responsive gatekeeper.