Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid hydroperoxides to lethal levels. YAP has been reported to play a pivotal role in controlling ferroptotic death, and the expression of YAP is enhanced and stabilized by O-GlcNAcylation. However, whether O-GlcNAcylation can increase the sensitivity of hepatocellular carcinoma (HCC) cells to ferroptosis remains unknown. In the present study, we found that O-GlcNAcylation increased the sensitivity of HCC cells to ferroptosis via YAP. Moreover, YAP increased the iron concentration in HCC cells through transcriptional elevation of TFRC via its O-GlcNAcylation. With YAP knockdown or YAP-T241 mutation, the increased sensitivity to ferroptosis induced by O-GlcNAcylation was abolished. In addition, the xenograft assay confirmed that O-GlcNAcylation increased ferroptosis sensitivity via TFRC in vivo. In summary, we are the first to find that O-GlcNAcylation can increase ferroptosis sensitivity in HCC cells via YAP/TFRC. Our work will provide a new basis for clinical therapeutic strategies for HCC patients.
Hypoxic-ischemic brain injury contributes to major neurodevelopmental disorders and is one of the leading causes of seizures which substantially results in neurodevelopmental impairments with long-lasting outcomes and is one of the main causes of death in neonates. We aimed to investigate the correlation between miRNA-210 and SCN1B, a voltage-gated sodium channel gene, in brain tissue of fetal rats with hypoxic-ischemic brain injury. We found that after 10 min of hypoxia-ischemia, all reperfusion groups showed different degrees of damage. The degree of the injury increased in all the groups after 30 min of hypoxia-ischemia. Those changes include changes in the pericellular lumen, capillaries in the cortex, erythrocytes, enlarged pericellular lumen, the enlarged pericapillary lumen in the cortex, edema around glial cells, enlarged gap to form multiple necrotic foci, deformation of neurons, and loss of cell structure. The expression levels of HIF-1α, miRNA-210, and HIF-1α mRNA were higher in the hypoxic-ischemic groups than that in the control groups, among which the expression levels in the severe group were higher than that in mild group. SCN1B is downregulated in both mild and severe groups, and the lowest level was found at 30 min after Hypoxia in both groups. MiRNA-210 plays a role in the development of HIE by regulating the expression changes of SCN1B. The brain tissue of fetal rats in the hypoxic-ischemic animal model showed pathological changes in brain injury.
Phosphorylation is one of the most important protein post‐translational modifications, which possesses dramatic regulatory effects on the function of proteins. In consideration of the low abundance and low stoichiometry of phosphorylation and non‐specific signal suppression, efficient capture of the phosphoproteins from complex biological samples is critical to meet the need for protein profiling. In this work, a facile preparation of titanium (IV)‐immobilized O‐phospho‐L‐tyrosine modified magnetic nanoparticles was developed for the enrichment of intact phosphoproteins. The prepared magnetic nanoparticles were characterized by various instruments and had a spherical shape with an average diameter of 300 nm. The adsorption isotherms were investigated and the maximum capacity for β‐casein was calculated to be 961.5 mg/g. Standard protein mixtures and biological samples (non‐fat milk and human serum) were selected to test the enrichment performance. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis demonstrated the excellent enrichment performance with high selectivity. With the superparamagnetic property, titanium (IV)‐immobilized O‐phospho‐L‐tyrosine modified magnetic nanoparticles were convenient for the practical application and clinical promotion, thus having a promising prospect in the field of phosphoprotein research.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.