Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4
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...
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Wolters Kluwer Medknow Publications
2021-01-01
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doaj-66d0e19352b747ffad1de0940637bcad2020-11-25T03:43:15ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742021-01-0116356156610.4103/1673-5374.293157Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4Bao-You FanYi-Lin PangWen-Xiang LiChen-Xi ZhaoYan ZhangXu WangGuang-Zhi NingXiao-Hong KongChang LiuXue YaoShi-Qing FengOur 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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=3;spage=561;epage=566;aulast=Fancell death; central nervous system; factor; ferroptosis; oligodendrocyte; oxidation; pathway; repair; spinal cord injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bao-You Fan Yi-Lin Pang Wen-Xiang Li Chen-Xi Zhao Yan Zhang Xu Wang Guang-Zhi Ning Xiao-Hong Kong Chang Liu Xue Yao Shi-Qing Feng |
spellingShingle |
Bao-You Fan Yi-Lin Pang Wen-Xiang Li Chen-Xi Zhao Yan Zhang Xu Wang Guang-Zhi Ning Xiao-Hong Kong Chang Liu Xue Yao Shi-Qing Feng Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 Neural Regeneration Research cell death; central nervous system; factor; ferroptosis; oligodendrocyte; oxidation; pathway; repair; spinal cord injury |
author_facet |
Bao-You Fan Yi-Lin Pang Wen-Xiang Li Chen-Xi Zhao Yan Zhang Xu Wang Guang-Zhi Ning Xiao-Hong Kong Chang Liu Xue Yao Shi-Qing Feng |
author_sort |
Bao-You Fan |
title |
Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 |
title_short |
Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 |
title_full |
Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 |
title_fullStr |
Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 |
title_full_unstemmed |
Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 |
title_sort |
liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4 |
publisher |
Wolters Kluwer Medknow Publications |
series |
Neural Regeneration Research |
issn |
1673-5374 |
publishDate |
2021-01-01 |
description |
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. |
topic |
cell death; central nervous system; factor; ferroptosis; oligodendrocyte; oxidation; pathway; repair; spinal cord injury |
url |
http://www.nrronline.org/article.asp?issn=1673-5374;year=2021;volume=16;issue=3;spage=561;epage=566;aulast=Fan |
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