PUBLICATION
Ferroptosis of brain microvascular endothelial cells contributes to hypoxia-induced blood-brain barrier injury
- Authors
- Liu, Q., Song, T., Chen, B., Zhang, J., Li, W.
- ID
- ZDB-PUB-230413-49
- Date
- 2023
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37: e22874e22874 (Journal)
- Registered Authors
- Zhang, Jingjing
- Keywords
- blood-brain barrier, brain microvascular endothelial cell, ferroptosis, hypoxia, zebrafish
- MeSH Terms
-
- 1-Acylglycerophosphocholine O-Acyltransferase
- Animals
- Blood-Brain Barrier*
- Brain
- Endothelial Cells
- Ferroptosis*
- Mice
- Zebrafish
- PubMed
- 37043308 Full text @ FASEB J.
Citation
Liu, Q., Song, T., Chen, B., Zhang, J., Li, W. (2023) Ferroptosis of brain microvascular endothelial cells contributes to hypoxia-induced blood-brain barrier injury. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 37:e22874e22874.
Abstract
Hypoxia is pivotal to the pathogeneses of myriad disorders, especially hypoxic cerebropathy. Much is known about the damage to the blood-brain barrier (BBB) in response to hypoxia. Studies have shown that endothelial cell death is closely linked to functional impairment of BBB. Mounting evidences have demonstrated that ferroptosis, a new pathway regulating cell death, is implicated in brain injury. However, whether ferroptosis is involved in hypoxia-induced BBB disruption remains ambiguous. Here, we utilized in vivo zebrafish and in vitro bEnd.3 cells to explore the correlation between endothelial ferroptosis and hypoxia-induced BBB damage. We found that hypoxic treatment for 45 min can induce BBB disruption by triggering down-regulation of claudin-5 (CLDN5) both in zebrafish cerebrovascluar endothelial cells and bEnd.3 cells. Besides, in vitro and in vivo studies revealed the cysteine/glutamate antiporter xCT (also known as solute carrier family 7 member 11; SLC7A11) decrease, glutathione peroxidase 4 (GPX4) and glutathione (GSH) reduction, 4-Hydroxynonenal (4-HNE) increasement, malondialdehyde (MDA) upregulation and reactive oxygen species (ROS) accumulation in hypoxia group. Further mechanism studies indicated that hypoxia-induced BBB damage might associate with microvascular endothelial cellular ferroptosis, since hypoxic exposure significantly activated the expression of ferroptosis-related genes (Ptgs2, Por, Lpcat3, Alox5, Alox12, Nfe2l2, and Ncoa4) and inhibited the expression of Slc7a11. Additionally, the application of 20 μM ferrostatin-1 (Fer-1), a ferroptosis inhibitor, could partially alleviate BBB disruption under hypoxia, suggesting that inhibition of ferroptosis might be a potential strategy for some neurological diseases with BBB defect.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping