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Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury

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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.

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Acknowledgments

This work was supported by grants from the Nantong University (Grant Codes: YKC15095) and Spine Surgery Clinical Medical Research Center (Grant Codes: HS2014002). We appreciate the technical assistances from M.M. Fang Liu in Jiangsu Province Key Laboratory of neural regeneration. We thank M.D. Aiguo Shen (Nantong University) for editing the language.

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    Authors and Affiliations

    1. Department of Spine Surgery, The Second Affiliated Hospital of Nantong University, Nantong University, Haier Lane North Road No. 6, Nantong, 226001, Jiangsu, China

      Chunshuai Wu, Jiajia Chen, Jinlong Zhang, Song Wang, Guofeng Bao, Guanhua Xu, Yuyu Sun, Lingling Wang, Limin Chen, Haiyan Gu, Baihong Cui & Zhiming Cui

    2. Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, 226001, Jiangsu, China

      Chunshuai Wu, Yonghua Liu, Wensen Ding, Song Wang & Zhiming Cui

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    Chunshuai Wu and Jiajia Chen have contributed equally to this work.

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    Wu, C., Chen, J., Liu, Y. et al. Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord Injury. Neurochem Res 41, 3103–3112 (2016). https://doi.org/10.1007/s11064-016-2033-7

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