Endoplasmic Reticulum Protein 29 Protects Cortical Neurons From Apoptosis and Promoting Corticospinal Tract Regeneration to Improve Neural Behavior via Caspase and Erk Signal in Rats with Spinal Cord Transection

Abstract

Following spinal cord injury (SCI), limit spontaneous functional recovery often emerged. However, the neuronal mechanisms associated with this phenomenon still remains obscure. By using proteomics analysis, endoplasmic reticulum protein 29 (ERp29) was discovered to increase in the motor cortexes of spinal cord transection (SCT) rats for 28 days post-operation (dpo) compared with in 14dpo. Then, the change in the expression of ERp29 was confirmed by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot. To determine the role of ERp29 in the recovery of locomotor functions following SCT, lentiviral vectors were used to up- and downregulate the expression level of ERp29. Here, we found that cortical neurons in vitro with high level of ERp29 expression exhibited a significant proliferation, characterized by smaller size of soma and more extensive axon outgrowth, compared with neurons used as control, while ERp29 silence got the opposite results. In vivo, Lentivirus was inject into the cerebral cortex following SCT at thoracic level 10, which resulted in an increase number of neuronal nuclei(NeuN)-positive cells and less apoptotic cells. Moreover, increased PKC-γ immunoreactivity density was also found in the spinal cord T9 level compared with control rats. This was associated with a great functional improvement, indicated by Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Lastly, we verified that ERp29 acts as a regulator by regulating a group of genes related with cell survival and apoptosis, involving in caspase and Erk, but not PI3K. Our findings showed that ERp29 can improve locomotor function by promoting neuronal survival and axonal regeneration in SCT rats via caspase and Erk signal pathway.

Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews

“…In order to identify the cultured BMSC and detect the expression of NTFs, corresponding primary and secondary antibodies (Table 2) for immunofluorescent staining were used following a previously reported protocol (Liu et al, 2014). Negative control was incubated with phosphate buffer saline (PBS) to replace the primary antibody.…”

Cellular prion protein mediates early apoptotic proteome alternation and phospho-modification in human neuroblastoma cells

“…For instance, endoplasmic reticulum (ER) stress-activated protein, ER-resident protein 29, a chaperone that facilitates protein processing and transport, 31 and appears to possess anti-apoptotic properties, 32 demonstrated an increased expression in PrP c -overexpressing versus control cells (both treated with STS). In earlier proteomic study, STS treatment of SH-SY5Y cells induced significant changes in endoplasmic reticulum proteins.…”

Molecular Chaperone ERp29: A Potential Target for Cellular Protection in Retinal and Neurodegenerative Diseases

“…ERp29, normally present at high levels in the brain, is down-regulated in rat motor cortex following spinal cord injury (SCI; Liu et al 2014). Intriguingly, lentiviral expression of ERp29 in cortex increases motor neuron survival and decreases apoptosis after SCI, while virally-mediated suppression of ERp29 increases cortical neuron death (Liu et al 2014).…”

“…ERp29, normally present at high levels in the brain, is down-regulated in rat motor cortex following spinal cord injury (SCI; Liu et al 2014). Intriguingly, lentiviral expression of ERp29 in cortex increases motor neuron survival and decreases apoptosis after SCI, while virally-mediated suppression of ERp29 increases cortical neuron death (Liu et al 2014). Remarkably, viral-mediated overexpression of ERp29 after SCI also results in marked improvement in motor function within weeks, suggesting a potential role for ERp29 in axon regeneration as well, potentially via its regulation of ERK pathways (Liu et al 2014).…”