ALAS2 Prevents Neonatal Necrotizing Enterocolitis by Improving Ferroptosis in Intestinal Epithelial Cells Through Inhibition of Oxidative Stress
Zenghui Hao, Jinbao Han, Ting Yao, Zheng Zhao, Wei Fan, Zaiqun Jiang, Yunting Wang, Xiaoqian Yang, Zhilin Xu
TL;DR
This study shows that ALAS2 protects against neonatal intestinal disease by reducing oxidative stress and cell death in intestinal cells.
Contribution
The study identifies ALAS2 as a novel therapeutic target for neonatal necrotizing enterocolitis by inhibiting ferroptosis.
Findings
ALAS2 expression is reduced in NEC-affected intestinal tissues and correlates with oxidative stress and ferroptosis.
Overexpression of ALAS2 in intestinal cells reduces necrosis and ferroptosis markers in vitro.
ALAS2 modulates nutrient and redox pathways, offering a potential treatment strategy for NEC.
Abstract
Neonatal necrotizing enterocolitis (NEC) is an intestinal disease that occurs in the neonatal period. The purpose of this study was to investigate the role of 5′‐aminolevulinate synthase 2 (ALAS2) in NEC‐induced intestinal injury. In a neonatal mouse, NEC model was induced by high‐osmolarity formula and hypoxia‐cold stress, and ALAS2 expression was significantly downregulated in ileal tissues (p < 0.01), coinciding with elevated oxidative stress (increased Fe2+/malondialdehyde [MDA] and decreased superoxide dismutase [SOD]), inflammation (increased TNF‐α/interferon‐gamma [IFN‐γ]), and ferroptosis activation (increased acyl‐CoA synthetase long‐chain family member 4 [ACSL4] and decreased ferritin heavy chain 1 [FTH1] with mitochondrial shrinkage). In vitro, tumor necrosis factor‐alpha (TNF‐α)/IFN‐γ‐treated intestinal epithelial cell (IEC) exhibited progressive ALAS2 suppression and…
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Taxonomy
TopicsInfant Nutrition and Health · Ferroptosis and cancer prognosis · Acute Lymphoblastic Leukemia research