Expression of Suppressor of Cytokine Signaling-3 (SOCS3) and its role in neuronal death after complete spinal cord injury
| Autor: | Keun W. Park, Ching Yi Lin, Yu Shang Lee |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Programmed cell death
Time Factors Suppressor of Cytokine Signaling Proteins Biology Transfection Article Rats Sprague-Dawley Small hairpin RNA Bcl-2-associated X protein Developmental Neuroscience Glial Fibrillary Acidic Protein medicine Animals Humans SOCS3 RNA Small Interfering Spinal cord injury Spinal Cord Injuries bcl-2-Associated X Protein Neurons Regulation of gene expression CD11b Antigen Cell Death Caspase 3 digestive oral and skin physiology medicine.disease Spinal cord Rats Cell biology Disease Models Animal HEK293 Cells medicine.anatomical_structure Gene Expression Regulation Neurology Suppressor of Cytokine Signaling 3 Protein Phosphopyruvate Hydratase Immunology biology.protein Female Signal transduction |
| Zdroj: | Experimental Neurology. 261:65-75 |
| ISSN: | 0014-4886 |
| Popis: | The present study investigates the endogenous expression of Suppressor of Cytokine Signaling-3 (SOCS3) after spinal cord injury (SCI) and its effect on SCI-induced cell death in vivo. In addition, we determined whether a reduction of SOCS3 expression induced by microinjection of short hairpin RNA (shSOCS3) carried by lentivirus into spinal cord provides cellular protection after SCI. We demonstrated that complete transection of rat T8 spinal cord induced SOCS3 expression at the mRNA and protein levels as early as 2 days post-injury, which was maintained up to 14 days. SOCS3 immunoreactivity was detected in neurons and activated microglia after SCI. We also demonstrated that SCI induces phosphorylation of proteins that are involved in signal transduction and transcription-3 (STAT3) in neurons, which induced SOCS3 expression. Western blot analyses and double-immunofluorescent staining showed significant up-regulation of the pro-apoptotic protein Bax, increases in the ratio of Bax to the anti-apoptotic protein Bcl-2, and up-regulation of cleaved caspase-3 in neurons. Treatment with shSOCS3 inhibited SCI-induced mRNA expression of SOCS3 2 days post-injury and suppressed SCI-induced Bax expression 7 days after SCI, both rostral and caudal to the lesion. Moreover, treatment with shSOCS3 inhibited SCI-induced neuronal death and protected neuronal morphology both rostral and caudal to the injury site 7 days post-injury. Our results suggest that the STAT3/SOCS3 signaling pathway plays an important role in regulating neuronal death after SCI. |
| Databáze: | OpenAIRE |
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