Upregulation of eIF-5A1 in the paralyzed muscle after spinal cord transection associates with spontaneous hindlimb locomotor recovery in rats by upregulation of the ErbB, MAPK and neurotrophin signal pathways

Shang, Fei; Zhao, Wei; Zhao, Qi; Liu, Jia; Li, Dawei; Zhang, Hua; Zhou, Xin‐Fu; Li, Chengyun; Wang, Ting‐Hua

doi:10.1016/j.jprot.2012.12.002

Cited by 13 publications

(29 citation statements)

References 32 publications

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“…The highly conserved module of MAPK cascade participates in a variety of cellular functions, including cell proliferation, differentiation and migration. Neuro- trophins belong to the category of trophic factors, which are involved in the differentiation, growth and survival of cells [31]. Several intracellular signaling pathways including the MAPK cascade would be stimulated by the activation of multiple ligands such as the epidermal growth factor (EGF) on ErbB receptor, which is regulated by Src [32].…”

Section: Resultsmentioning

confidence: 99%

A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1

Liu

Zhang

et al. 2016

Aging

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The mutation of somitogenesis protein Mesogenin 1 (Msgn1) has been widely used to study the direct link between somitogenesis and the development of an embryo. Several studies have used gene expression profiling of somitogenesis to identify the key genes in the process, but few have focused on the pathways involved and the coexpression patterns of associated pathways. Here we employed time-course microarray datasets of differentiating embryonic stem cells by overexpressing the transcription factor Msgn1 from the public database library of Gene Expression Omnibus (GEO). Then we applied gene set enrichment analysis (GSEA) to the datasets and performed candidate transcription factors selection. As a result, several significantly regulated pathways and transcription factors (TFs), as well as some of the specific signaling pathways, were identified during somitogenesis under Msgn1 overexpression, most of which had not been reported previously. Finally, significant core genes such as Hes1 and Notch1 as well as some of the TFs such as PPARs and FOXs were identified to construct coexpression networks of related pathways, the expression patterns of which had been validated by our following quantitative real-time PCR (qRT-PCR). The results of our study may help us better understand the molecular mechanisms of somitogenesis in mice at the genome-wide level.

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Section: Resultsmentioning

confidence: 99%

A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1

Liu

Zhang

et al. 2016

Aging

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“…S1A–C . The sequence for the eIF5A1 shRNA vector was obtained from a previous study 17 . Additional vector information and expression of the appropriate reporter genes are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Axonal damage at the epicenter of pathologies such as stroke, traumatic brain injury (TBI) and SCI patients can result in signal conduction failure at the epicenter of their pathology due to which in turn causes persistent functional deficit. Restoration of neurological functions or neuroplasticity does occur in these CNS pathologies but it is limited 1 3 12 13 17 . A potential mechanism to induce neuroplasticity may be involved creating remodeling the local circuitry in the spinal cord 6 13 17 28 .…”

Section: Discussionmentioning

confidence: 99%

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

Liu

Shang

et al. 2015

Sci Rep

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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.

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“…As described previously (Shang et al, 2013), the RNA was extracted by Trizol reagent (Invitrogen). Complete description of RNA extraction and PCR analysis can be found in the Supplementary Methods.…”

Section: Rna Extraction and Pcr Analysismentioning

confidence: 99%

Role of Nicotinamide N-Methyltransferase in Dorsal Striatum in Cocaine Place Preference

Luo

Shang

Long

et al. 2017

Neuropsychopharmacol

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Nicotinamide N-methyltransferase (NNMT) transfers the methyl from S-adenosyl-L-methionine (SAM) to nicotinamide (NA) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide (MeN). NNMT has been implicated in a variety of diseases; however, the role of NNMT in drug addiction is largely unknown. Here, we found that the expression of Nnmt was significantly upregulated in the dorsal striatum (DS) of cocaine-conditioned mice. Cocaine significantly decreased SAM/SAH ratio levels in the DS, which was accompanied with the decreased activities of Rac1 and RhoA. Lentivirus-mediated knockdown of Nnmt in the dorsomedial striatum (DMS) attenuated cocaine conditioned place preference (CPP) reward, but increased striatal SAM/SAH ratio levels as well as Rac1 and RhoA activities. In addition, pharmacological inhibition of NNMT through intra-DMS infusion of MeN attenuated cocaine CPP and the activities of Rac1 and RhoA, but increased SAM/SAH ratio. These results suggest that NNMT-dependent transmethylation is involved in the activation of Rac1 and RhoA, which utilize SAM as a methyl donor cofactor. Co-immunoprecipitation assay using a RhoGDIα antibody indirectly captured Rac1 or RhoA that were bound to RhoGDIα. The results showed that cocaine increased the association of RhoGDIα with Rac1 or RhoA, whereas such effect was inhibited by Nnmt knockdown. Collectively, our findings show that NNMT regulates cocaine CPP through SAM-mediated modification of Rac1 and RhoA.

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Upregulation of eIF-5A1 in the paralyzed muscle after spinal cord transection associates with spontaneous hindlimb locomotor recovery in rats by upregulation of the ErbB, MAPK and neurotrophin signal pathways

Cited by 13 publications

References 32 publications

A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1

A comprehensive transcriptomic analysis of differentiating embryonic stem cells in response to the overexpression of Mesogenin 1

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

Role of Nicotinamide N-Methyltransferase in Dorsal Striatum in Cocaine Place Preference

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