title: Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury.
abstract: 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-α (TNF-α) induced necroptosis cell model. Based on our experimental data, we boldly conclude that PSMB4 is associated with RIP3 involved necroptosis after SCI.
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
authors: Chunshuai
authors: C
authors: Wu
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Jiajia
authors: J
authors: Chen
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
authors: Yonghua
authors: Y
authors: Liu
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Jinlong
authors: J
authors: Zhang
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
authors: Wensen
authors: W
authors: Ding
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
authors: Song
authors: S
authors: Wang
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Guofeng
authors: G
authors: Bao
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Guanhua
authors: G
authors: Xu
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Yuyu
authors: Y
authors: Sun
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Lingling
authors: L
authors: Wang
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Limin
authors: L
authors: Chen
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Haiyan
authors: H
authors: Gu
authors: Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China.
authors: Baihong
authors: B
authors: Cui
authors: 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.|Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China. zhimingcui@126.com.
authors: Zhiming
authors: Z
authors: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D015533:Transcriptional Activation / Q000502:physiology; D015854:Up-Regulation
chemical_list: D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; C000610190:PSMB4 protein, rat; D046988:Proteasome Endopeptidase Complex
keywords: MLKL; Necroptosis; PSMB4; RIP3; SCI; TNF-α