Spermine is an endogenous iron chelator that inhibits ferroptosis - PubMed
2 hours ago
- #iron-chelator
- #ferroptosis
- #spermine
- Spermine, an endogenous polyamine derived from spermidine, acts as an iron chelator to directly inhibit ferroptosis by limiting iron availability and lipid peroxidation.
- ALDH18A1 facilitates an alternative glutamine-dependent pathway for de novo spermine synthesis, which is crucial in suppressing ferroptosis in hepatocellular carcinoma.
- Inhibition of ALDH18A1 (via knockout, shRNA, or inhibitor YG1702) promotes ferroptosis and hinders hepatocarcinogenesis, both spontaneous and chemically induced.
- Spermine supplementation provides protection against ferroptosis-associated tissue damage, such as ischemia-reperfusion injury in the liver, intestine, and kidneys.
- The study identifies spermine-mediated iron chelation as a key metabolic circuit in regulating ferroptosis, with implications for cancer and tissue injury treatment.