Cold-inducible RNA binding protein alleviates iron overload-induced neural ferroptosis under perinatal hypoxia insult.
Cell Death Differ
; 31(4): 524-539, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38388728
ABSTRACT
Cold-inducible RNA binding protein (CIRBP), a stress response protein, protects cells from mild hypothermia or hypoxia by stabilizing specific mRNAs and promoting their translation. Neurons subjected to hypobaric hypoxia insult trigger various cell death programs. One of these is ferroptosis, a novel non-apoptotic form of programmed cell death, which is characterized by excessive iron ion accumulation and lipid peroxidation. Here, we establish that CIRBP can regulate neuronal ferroptosis both in vivo and in vitro. We observe that hypoxia leads to neuronal death via intracellular ferrous iron overload and impaired antioxidant systems, accompanied by suppressed CIRBP expression. Genetic enrichment of CIRBP in hippocampal neurons CIRBPTg mice bred with Emx1-Cre mice attenuates hypoxia-induced cognitive deficits and neuronal degeneration. Mechanistically, CIRBP alleviates neuronal ferroptosis and intracellular ferrous ion accumulation by binding to the mitochondrial ferritin (FTMT) 3'UTR to stabilize mRNA and promote its translation. Our novel study shows the critical role of CIRBP in the progression of ferroptosis, and provides promising therapeutic target for hypoxia-induced neurological diseases.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Unión al ARN
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Sobrecarga de Hierro
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Ferroptosis
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Neuronas
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Death Differ
Año:
2024
Tipo del documento:
Article
País de afiliación:
China