Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury
Ferroptosis is one of the critical pathological events in spinal cord injury. Erythropoietin has been reported to improve the recovery of spinal cord injury. However, whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined. In this...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2023-01-01
|
| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=881;epage=888;aulast=Kang |
| _version_ | 1798021669724356608 |
|---|---|
| author | Yu Kang Rui Zhu Shuang Li Kun-Peng Qin Hao Tang Wen-Shan Shan Zong-Sheng Yin |
| author_facet | Yu Kang Rui Zhu Shuang Li Kun-Peng Qin Hao Tang Wen-Shan Shan Zong-Sheng Yin |
| author_sort | Yu Kang |
| collection | DOAJ |
| description | Ferroptosis is one of the critical pathological events in spinal cord injury. Erythropoietin has been reported to improve the recovery of spinal cord injury. However, whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined. In this study, we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks. Both low and high doses of erythropoietin promoted recovery of hindlimb function, and the high dose of erythropoietin led to better outcome. High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin. The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1 (a ferroptosis suppressor), and the effects of erythropoietin were largely diminished by RSL3 (ferroptosis activator). In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4. This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury. Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury. |
| first_indexed | 2024-04-11T17:17:20Z |
| format | Article |
| id | doaj.art-d14e145fd4424ba395953a1ce4003318 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-11T17:17:20Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-d14e145fd4424ba395953a1ce40033182022-12-22T04:12:36ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-0118488188810.4103/1673-5374.353496Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injuryYu KangRui ZhuShuang LiKun-Peng QinHao TangWen-Shan ShanZong-Sheng YinFerroptosis is one of the critical pathological events in spinal cord injury. Erythropoietin has been reported to improve the recovery of spinal cord injury. However, whether ferroptosis is involved in the neuroprotective effects of erythropoietin on spinal cord injury has not been examined. In this study, we established rat models of spinal cord injury by modified Allen’s method and intraperitoneally administered 1000 and 5000 IU/kg erythropoietin once a week for 2 successive weeks. Both low and high doses of erythropoietin promoted recovery of hindlimb function, and the high dose of erythropoietin led to better outcome. High dose of erythropoietin exhibited a stronger suppressive effect on ferroptosis relative to the low dose of erythropoietin. The effects of erythropoietin on inhibiting ferroptosis-related protein expression and restoring mitochondrial morphology were similar to those of Fer-1 (a ferroptosis suppressor), and the effects of erythropoietin were largely diminished by RSL3 (ferroptosis activator). In vitro experiments showed that erythropoietin inhibited RSL3-induced ferroptosis in PC12 cells and increased the expression of xCT and Gpx4. This suggests that xCT and Gpx4 are involved in the neuroprotective effects of erythropoietin on spinal cord injury. Our findings reveal the underlying anti-ferroptosis role of erythropoietin and provide a potential therapeutic strategy for treating spinal cord injury.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=881;epage=888;aulast=Kangerythropoietin; ferroptosis; gpx4; iron overload; lipid peroxidation; mechanism; neurological function recovery; spinal cord injury; spinal neuron; xct |
| spellingShingle | Yu Kang Rui Zhu Shuang Li Kun-Peng Qin Hao Tang Wen-Shan Shan Zong-Sheng Yin Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury Neural Regeneration Research erythropoietin; ferroptosis; gpx4; iron overload; lipid peroxidation; mechanism; neurological function recovery; spinal cord injury; spinal neuron; xct |
| title | Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury |
| title_full | Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury |
| title_fullStr | Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury |
| title_full_unstemmed | Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury |
| title_short | Erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury |
| title_sort | erythropoietin inhibits ferroptosis and ameliorates neurological function after spinal cord injury |
| topic | erythropoietin; ferroptosis; gpx4; iron overload; lipid peroxidation; mechanism; neurological function recovery; spinal cord injury; spinal neuron; xct |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=4;spage=881;epage=888;aulast=Kang |
| work_keys_str_mv | AT yukang erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury AT ruizhu erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury AT shuangli erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury AT kunpengqin erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury AT haotang erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury AT wenshanshan erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury AT zongshengyin erythropoietininhibitsferroptosisandamelioratesneurologicalfunctionafterspinalcordinjury |