NDRG2 regulates glucose metabolism and ferroptosis of OGD/R‐treated astrocytes by the Wnt/β‐catenin signaling

作者：Lin Wu, Yingying Cheng, Runfeng Wang, Shukai Sun, Bo Ma, Zhiguo Zhang · 发表于：Journal of Biochemical and Molecular Toxicology · 年份：2024 · DOI：10.1002/jbt.23827 · 被引用次数：15 · 研究领域：Mechanisms of cancer metastasis、Ferroptosis and cancer prognosis、Trace Elements in Health

Abstract Ischemic stroke is one main type of cerebrovascular disorders with leading cause of death and disability worldwide. Astrocytes are the only nerve cell type storing glycogen in the brain, which regulate the glucose metabolism and handle the energy supply and survive of neurons. Astrocyte ferroptosis contributes to neuron injury in brain disorders. N‐myc downstream‐regulated gene 2 (NDRG2) has been implicated in the progression of brain diseases, including ischemic stroke. However, whether NDRG2 could affect the glucose metabolism and ferroptosis of astrocytes during ischemic stroke remains largely unknown. Mouse astrocytes were treated with oxygen‐glucose deprivation/reoxygenation (OGD/R) to establish the in vitro model. Glial fibrillary acidic protein, NDRG2, Wnt3a and β‐catenin expression levels were detected by immunofluorescence staining and western blot analyses. Glucose metabolism was investigated by glucose uptake, lactate production, nicotinamide adenine dinucleotide phosphate hydrogen/nicotinamide adenine dinucleotide phosphate (NADPH/NADP + ), ATP and glycolysis enzymes (HK2, PKM2 and lactate dehydrogenase A [LDHA]) levels. Ferroptosis was assessed via reactive oxygen species (ROS), glutathione (GSH), iron and ferroptosis‐related markers (GPX4 and PTGS2) contents. Glycolysis enzymes and ferroptosis‐related markers levels were measured via western blot. NDRG2 expression was elevated in OGD/R‐induced astrocytes. NDRG2 overexpression aggravated OGD/R‐induced lo...