eIF5A1/RhoGDIα pathway: a novel therapeutic target for treatment of spinal cord injury identified by a proteomics approach

Wei Liu; Fei-Fei Shang; Yang Xu; Visar Belegu; Lei Xia; Wei Zhao; Ran Liu; Wei Wang; Jin Liu; Chen-Yun Li; Ting-Hua Wang

doi:10.1038/srep16911

eIF5A1/RhoGDIα pathway: a novel therapeutic target for treatment of spinal cord injury identified by a proteomics approach

Sci Rep. 2015 Nov 23:5:16911. doi: 10.1038/srep16911.

Authors

Wei Liu¹, Fei-Fei Shang¹, Yang Xu¹, Visar Belegu², Lei Xia¹, Wei Zhao¹, Ran Liu¹, Wei Wang¹, Jin Liu¹, Chen-Yun Li³, Ting-Hua Wang^{1

4}

Affiliations

¹ 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.
² Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
³ Key Laboratory of Agro-Biodiversity and Pest Management of Education Ministry of China, Yunnan Agricultural University, Kunming, 650000, P.R. China.
⁴ Institute of Neuroscience, Kunming medical University, Kunming 650031, P.R. China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Cell Line
Cell Proliferation / genetics
Cell Survival / genetics
Cytoskeleton / metabolism
Cytoskeleton / ultrastructure
Eukaryotic Translation Initiation Factor 5A
Female
Gene Expression Regulation
Humans
Molecular Sequence Data
Motor Activity / physiology
Neurons / metabolism
Neurons / ultrastructure
Peptide Initiation Factors / antagonists & inhibitors
Peptide Initiation Factors / genetics*
Peptide Initiation Factors / metabolism
Primary Cell Culture
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
RNA-Binding Proteins / antagonists & inhibitors
RNA-Binding Proteins / genetics*
RNA-Binding Proteins / metabolism
Rats
Rats, Sprague-Dawley
Recovery of Function / physiology*
Remission, Spontaneous
Signal Transduction / genetics*
Spinal Cord / metabolism
Spinal Cord / pathology
Spinal Cord Injuries / genetics*
Spinal Cord Injuries / metabolism
Spinal Cord Injuries / pathology
rho Guanine Nucleotide Dissociation Inhibitor alpha / antagonists & inhibitors
rho Guanine Nucleotide Dissociation Inhibitor alpha / genetics*
rho Guanine Nucleotide Dissociation Inhibitor alpha / metabolism

Substances

Peptide Initiation Factors
RNA, Small Interfering
RNA-Binding Proteins
rho Guanine Nucleotide Dissociation Inhibitor alpha