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• W2078682633 abstract "Spinal cord injury (SCI) can lead to paraplegia or quadriplegia, and exhibit significant spontaneous functional recovery. The underlying mechanisms remain elusive. Proteomics analysis revealed differential protein spots in the gastrocnemius muscle between spinal cord transection (SCT) and normal rats. siRNA was used to down-regulate the mRNA level of eIF-5A1 and observed neuromuscular junction (NMJ) formation, hindlimb locomotor functional recovery and bioinformatics analysis of mRNA expression in microarray in SCT rats. In the SCT rat's gastrocnemius, DNA demethylation was observed around the promoter region of eIF-5A1 by using High Resolution Melting (HRM) technology. Spinal cord injury (SCI) can lead to paraplegia or quadriplegia, and exhibit significant spontaneous functional recovery. The mechanisms underlying spontaneous plasticity of the neuronal circuitry are not well understood. While most studies focus on the regeneration of fiber tracts in the spinal cord, little is known about changes in the skeletal muscles like the gastrocnemius, which are expected to be affected by the cord transection. Eukaryotic initiation factor 5A (eIF5A), unique protein that N-terminal lysine been post-translationally modified to hypusine. As the only cellular protein that contains the unusual amino acid, hypusine [N(ε)-(4-amino-2-hydroxybutyl) lysine], it has been implicated in multiple cellular functions including translation initiation, translation elongation, cell cycle, cell survival. Many biological processes are not only determined by DNA code itself, but also regulated by activity-related chromosomal remodeling. Epigenetic modification such as DNA methylation plays essential roles in cellular differentiation and proliferation. Neuromuscular junction (NMJ) is the synapses whereby spinal motor neurons (MN) control the contraction of skeletal muscles. During the formation of vertebrate NMJs, signals from presynaptic motor neurons are necessary for the regulation of gene expression of postsynaptic transmitter receptors, which are acetylcholine receptors (AChRs). normal rats and spinal cord transection (SCT) rats. spinal cord transection model of rats; RNAi; differential protein spots in the gastrocnemius muscle between spinal cord transection (SCT) and normal rats were measured by Proteomics analysis. eIF-5A1 expression (mRNA and protein level) by RT-PCR, western-bloting; After injection siRNA of eIF-5A1 in SCT rats' gastrocnemius, gene expression microarrays and bioinformatics analysis showed signal pathways that is high correlation with eIF-5A1. DNA methylation level was detected by High Resolution Melting (HRM) technology; immunofluorescence and mRNA level of acetylcholine receptors (ACHR) was confirmed neuromuscular junction (NMJ) formation. Proteomics analysis revealed differential protein spots in the gastrocnemius muscle between spinal cord transection (SCT) and normal rats. Eukaryotic translation initiation factor 5A1 (elf-5A1), a highly conserved molecule throughout eukaryotes that is essential for the initiation and elongation step of translation, exhibited marked up-regulation in the rats’ gastrocnemius muscle after SCT. Then we used siRNA to down-regulate the mRNA level of eIF-5A1 and observed neuromuscular junction (NMJ) formation, hindlimb locomotor functional recovery and genes expression in SCT rats. Compared with untreated SCT control rats, those subjected to eIF-5A1 knockdown exhibited repressed formation of NMJ and impaired locomotor functional recovery. Gene expression microarrays and bioinformatics analysis showed that eIF-5A1 promote spontaneous hindlimb locomotor functional recovery via three main signal pathways (ErbB, MAPK and Neurotrophin signal pathway). To explain the overexpression of eIF-5A1, DNA demethylation was observed around the promoter region of eIF-5A1 by using High Resolution Melting (HRM) technology. In conclusion, the eIF-5A1 is suffered DNA demethylation in SCT rat’s gastrocnemius following SCT. Up-regulating of eIF-5A1 can increase NMJs formation to promote locomotor function recovery, and the possible mechanism is regulated by three main signal pathways (ErbB, MAPK and Neurotrophin signal pathway). So far, this is the first to report the change of DNA methylation level after SCT, especially in gastrocnemius. Our research could pave the way for the development of a new strategy for the treatment of spinal cord injury in clinical trials." @default.
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• W2078682633 date "2013-10-01" @default.
• W2078682633 modified "2023-09-27" @default.
• W2078682633 title "Poster 32 eIF-5A1 is a Crucial Molecule Promote Locomotor Function in Rat’s Gastrocnemius After Spinal Cord Transection" @default.
• W2078682633 doi "https://doi.org/10.1016/j.apmr.2013.08.078" @default.
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