title: Expression of suppressor of cytokine signaling-3 (SOCS3) and its role in neuronal death after complete spinal cord injury.
abstract: 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 2days post-injury, which was maintained up to 14days. 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 2days post-injury and suppressed SCI-induced Bax expression 7days 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 7days post-injury. Our results suggest that the STAT3/SOCS3 signaling pathway plays an important role in regulating neuronal death after SCI.
authors: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Keun Woo
authors: KW
authors: Park
authors: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Ching-Yi
authors: CY
authors: Lin
authors: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: leey2@ccf.org.
authors: Yu-Shang
authors: YS
authors: Lee
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D034741:RNA, Small Interfering; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase
keywords: Bax/Bcl-2; Neuronal death; Neuroplasticity; Short hairpin RNA; Spinal cord injury; Suppressor of Cytokine Signaling-3