Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4
Objective Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the im...
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Korean Spinal Neurosurgery Society
2025-03-01
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| Series: | Neurospine |
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| Online Access: | http://e-neurospine.org/upload/pdf/ns-2448878-439.pdf |
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| author | Hao Feng Dehui Chen Huina Chen Dingwei Wu Dandan Wang Zhengxi Yu Linquan Zhou Zhenyu Wang Wenge Liu |
| author_facet | Hao Feng Dehui Chen Huina Chen Dingwei Wu Dandan Wang Zhengxi Yu Linquan Zhou Zhenyu Wang Wenge Liu |
| author_sort | Hao Feng |
| collection | DOAJ |
| description | Objective Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair. |
| format | Article |
| id | doaj-art-63dfd188842d4e8b901458adb2d2ecfb |
| institution | DOAJ |
| issn | 2586-6583 2586-6591 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Korean Spinal Neurosurgery Society |
| record_format | Article |
| series | Neurospine |
| spelling | doaj-art-63dfd188842d4e8b901458adb2d2ecfb2025-08-20T03:06:14ZengKorean Spinal Neurosurgery SocietyNeurospine2586-65832586-65912025-03-0122115717210.14245/ns.2448878.4391665Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4Hao Feng0Dehui Chen1Huina Chen2Dingwei Wu3Dandan Wang4Zhengxi Yu5Linquan Zhou6Zhenyu Wang7Wenge Liu8 Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China School of Health, Fujian Medical University, Fuzhou, China Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China Wenzhou Business College, Wenzhou, China Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, China Department of Orthopedics, Fujian Medical University Union Hospital, Fuzhou, ChinaObjective Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.http://e-neurospine.org/upload/pdf/ns-2448878-439.pdfspinal cord injuryextracellular ubiquitincxcr4autophagymitochondrial apoptosis pathway |
| spellingShingle | Hao Feng Dehui Chen Huina Chen Dingwei Wu Dandan Wang Zhengxi Yu Linquan Zhou Zhenyu Wang Wenge Liu Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4 Neurospine spinal cord injury extracellular ubiquitin cxcr4 autophagy mitochondrial apoptosis pathway |
| title | Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4 |
| title_full | Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4 |
| title_fullStr | Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4 |
| title_full_unstemmed | Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4 |
| title_short | Extracellular Ubiquitin Enhances Autophagy and Inhibits Mitochondrial Apoptosis Pathway to Protect Neurons Against Spinal Cord Ischemic Injury via CXCR4 |
| title_sort | extracellular ubiquitin enhances autophagy and inhibits mitochondrial apoptosis pathway to protect neurons against spinal cord ischemic injury via cxcr4 |
| topic | spinal cord injury extracellular ubiquitin cxcr4 autophagy mitochondrial apoptosis pathway |
| url | http://e-neurospine.org/upload/pdf/ns-2448878-439.pdf |
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