title: eIF5A1/RhoGDIα pathway: a novel therapeutic target for treatment of spinal cord injury identified by a proteomics approach.
abstract: 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.
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Shang
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Visar
authors.initials: V
authors.lastname: Belegu
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Agro-Biodiversity and Pest Management of Education Ministry of China, Yunnan Agricultural University, Kunming, 650000, P.R. China.
authors.forename: Chen-Yun
authors.initials: CY
authors.lastname: Li
authors.affiliation: Institute of Neurological Disease, The state key laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 61041, P.R. China.|Institute of Neuroscience, Kunming medical University, Kunming 650031, P.R. China.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D010448:Peptide Initiation Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012075:Remission, Spontaneous; D015398:Signal Transduction / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D000097574:Eukaryotic Translation Initiation Factor 5A