eIF5A1/RhoGDIα pathway: a novel therapeutic target for treatment of spinal cord injury identified by a proteomics approach
| Autor: | Visar Belegu, Jin Liu, Yang Xu, Fei-Fei Shang, Chen-Yun Li, Wei Wang, Ting-Hua Wang, Lei Xia, Wei Liu, Wei Zhao, Ran Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Neurite
Cell Survival Molecular Sequence Data Primary Cell Culture Remission Spontaneous Biology Motor Activity Article Cell Line Rats Sprague-Dawley In vivo Peptide Initiation Factors medicine Initiation factor Animals Humans Amino Acid Sequence RNA Small Interfering Spinal cord injury Cytoskeleton Spinal Cord Injuries Cell Proliferation Neurons rho Guanine Nucleotide Dissociation Inhibitor alpha Gene knockdown Multidisciplinary Cell growth RNA-Binding Proteins Recovery of Function medicine.disease Spinal cord Molecular biology Cell biology Rats medicine.anatomical_structure Gene Expression Regulation Spinal Cord Female Signal transduction Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep16911 |
| Popis: | Spinal cord injury (SCI) is frequently accompanied by a degree of spontaneous functional recovery. The underlying mechanisms through which such recovery is generated remain elusive. In this study, we observed a significant spontaneous motor function recovery 14 to 28 days after spinal cord transection (SCT) in rats. Using a comparative proteomics approach, caudal to the injury, we detected difference in 20 proteins. Two of these proteins, are eukaryotic translation initiation factor 5A1 (eIF5A1) that is involved in cell survival and proliferation and Rho GDP dissociation inhibitor alpha (RhoGDIα), a member of Rho GDI family that is involved in cytoskeletal reorganization. After confirming the changes in expression levels of these two proteins following SCT, we showed that in vivo eIF5A1 up-regulation and down-regulation significantly increased and decreased, respectively, motor function recovery. In vitro, eIF5A1 overexpression in primary neurons increased cell survival and elongated neurite length while eIF5A1 knockdown reversed these results. We found that RhoGDIα up-regulation and down-regulation rescues the effect of eIF5A1 down-regulation and up-regulation both in vivo and in vitro. Therefore, we have identified eIF5A1/RhoGDIα pathway as a new therapeutic target for treatment of spinal cord injured patients. |
| Databáze: | OpenAIRE |
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