Journal
NEURAL REGENERATION RESEARCH
Volume 16, Issue 3, Pages 561-566Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.293157
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [81672171, 81972074, 81930070, 81620108018, 81772342]
- National Key R&D Program of China [2019YFA0112100]
- Natural Science Foundation of Tianjin of China [19JCZDJC34900]
Ask authors/readers for more resources
Our previous study highlighted the significance of ferroptosis in spinal cord injury. We established an oligodendrocyte model induced by RSL-3 inhibition of GPX4, which increased ROS levels and malondialdehyde concentrations. Additionally, we found that Liproxstatin-1 was a potent inhibitor of ferroptosis in oligodendrocytes, suggesting its potential as a treatment for CNS diseases.
Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury. High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma. In this study, we established an oligodendrocyte (OLN-93 cell line) model of ferroptosis induced by RSL-3, an inhibitor of glutathione peroxidase 4 (GPX4). RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde. RSL-3 also inhibited the main anti-ferroptosis pathway, i.e., SLC7A11/glutathione/glutathione peroxidase 4 (xCT/GSH/GPX4), and downregulated acyl-coenzyme A synthetase long chain family member 4. Furthermore, we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis. Liproxstatin-1 was more potent than edaravone or deferoxamine. Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation, but also restored the expression of GSH, GPX4 and ferroptosis suppressor protein 1. These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes, and that liproxstatin-1 is a potent inhibitor of ferroptosis. Therefore, liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available