Heme induces intestinal epithelial cell ferroptosis via mitochondrial dysfunction in transfusion-associated necrotizing enterocolitis.
FASEB J
; 36(12): e22649, 2022 12.
Article
em En
| MEDLINE
| ID: mdl-36383399
Transfusion-associated necrotising enterocolitis (TANEC) is a life-threatening disease with a poor prognosis in preterm infants. This study explored whether and how heme induces ferroptosis in TANEC gut injury. A TANEC mouse model and a cell culture system for heme and Caco-2 cells were established. Ferroptosis was assessed by measuring iron and malondialdehyde (MDA) levels and mitochondrial morphology in intestinal tissues and Caco-2 cells. Mitochondrial dysfunction was evaluated by measuring mitochondrial reactive oxygen species (ROS) production and membrane potential using JC-1. The intestinal injury grade was higher in the anemia-transfusion group than in the control group (p < .0001). Higher intestinal iron concentration (p < .0001), elevated levels of lipid peroxidation MDA (p = .0021), and ferroptotic mitochondrial morphological changes were found in mice of the anemia-transfusion group; specific ferroptosis inhibitor could alleviate anemia-transfusion gut injury, suggesting that ferroptosis play a role in the TANEC gut injury. Next, we explored whether heme released by hemolysis of erythrocytes induces ferroptosis in intestinal epithelial cells in vitro. The viability of Caco-2 cells significantly decreased after heme treatment (p < .0001). Iron accumulation, MDA elevated levels, and mitochondrial dysfunction also existed in the co-culture system, which ferroptosis inhibitors could reduce. In summary, ferroptosis was discovered in TANEC, and heme could induce ferroptosis in intestinal epithelial cells via mitochondrial dysfunction. Heme-inducing ferroptosis may be a possible mechanism and therapeutic target for TANEC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enterocolite Necrosante
/
Ferroptose
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
/
Newborn
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China