PMID- 27514644 OWN - NLM STAT- MEDLINE DCOM- 20170405 LR - 20231213 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 41 IP - 11 DP - 2016 Nov TI - Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury. PG - 3103-3112 AB - Spinal cord injury (SCI) is one of the most common and severe complications in spine injury. It is difficult to prevent cell necroptosis and promote the survival of residual neurons after SCI. Proteasome beta-4 subunit (PSMB4) is the first proteasomal subunit with oncogenic properties promoting cancer cell survival and tumor growth in vivo, and our previous study showed that PSMB4 is significantly associated with neuronal apoptosis in neuroinflammation. However, PSMB4 function in the necroptosis after SCI is unkown. RIP3, a key regulatory factor of necroptosis, correlates with the induction of necroptosis in various types of cells and signaling pathway. Upregulation of the RIP3 expression may play a role as a novel molecular mechanism in secondary neural tissue damage following SCI. In this study, we established an acute spinal cord contusion injury model in adult rats to investigate the potential role of PSMB4 during the pathological process of SCI. We found PSMB4 expression was significantly up-regulated 3 days after injury by western blot and immunohistochemical staining. Double immunofluorescent staining indicated obvious changes of PSMB4 expression occurred in neurons. Significant up-regulation of PSMB4 expression was observed in Rip3 positive neurons at 3 days after SCI, which indicated that PSMB4 might play a vital role in the regulation of Rip3. Overexpress and knockdown PSMB4 could intervene the RIP3 and Mixed lineage kinase domain-like protein (MLKL) pathway in Tumor necrosis factor-alpha (TNF-alpha) induced necroptosis cell model. Based on our experimental data, we boldly conclude that PSMB4 is associated with RIP3 involved necroptosis after SCI. FAU - Wu, Chunshuai AU - Wu C AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Chen, Jiajia AU - Chen J AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Liu, Yonghua AU - Liu Y AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Zhang, Jinlong AU - Zhang J AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Ding, Wensen AU - Ding W AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Wang, Song AU - Wang S AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. FAU - Bao, Guofeng AU - Bao G AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Xu, Guanhua AU - Xu G AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Sun, Yuyu AU - Sun Y AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Wang, Lingling AU - Wang L AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Chen, Limin AU - Chen L AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Gu, Haiyan AU - Gu H AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Cui, Baihong AU - Cui B AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. FAU - Cui, Zhiming AU - Cui Z AD - Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China. zhimingcui@126.com. AD - Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. zhimingcui@126.com. LA - eng PT - Journal Article DEP - 20160811 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Ripk3 protein, rat) RN - EC 3.4.22.- (PSMB4 protein, rat) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Disease Models, Animal MH - Male MH - Necrosis MH - Neurons/*metabolism MH - Proteasome Endopeptidase Complex/*metabolism MH - Rats, Sprague-Dawley MH - Receptor-Interacting Protein Serine-Threonine Kinases/*metabolism MH - Signal Transduction/physiology MH - Spinal Cord Injuries/*metabolism/physiopathology MH - Transcriptional Activation/physiology MH - Up-Regulation OTO - NOTNLM OT - MLKL OT - Necroptosis OT - PSMB4 OT - RIP3 OT - SCI OT - TNF-alpha EDAT- 2016/11/04 06:00 MHDA- 2017/04/06 06:00 CRDT- 2016/08/13 06:00 PHST- 2016/04/12 00:00 [received] PHST- 2016/08/05 00:00 [accepted] PHST- 2016/07/24 00:00 [revised] PHST- 2016/11/04 06:00 [pubmed] PHST- 2017/04/06 06:00 [medline] PHST- 2016/08/13 06:00 [entrez] AID - 10.1007/s11064-016-2033-7 [pii] AID - 10.1007/s11064-016-2033-7 [doi] PST - ppublish SO - Neurochem Res. 2016 Nov;41(11):3103-3112. doi: 10.1007/s11064-016-2033-7. Epub 2016 Aug 11.