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KPC1 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat

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Abstract

KPC1 (Kip1 ubiquitylation-promoting complex 1) is the catalytic subunit of the ubiquitin ligase KPC, which regulates the degradation of the cyclin-dependent kinase inhibitor p27kip1 at the G1 phase of the cell cycle. To elucidate the expression and role of KPC1 in nervous system lesion and repair, we performed an acute spinal cord contusion injury (SCI) model in adult rats. Western blot analysis showed a significant up-regulation of KPC1 and a concomitant down-regulation of p27kip1 following spinal injury. Immunohistochemistry and immunofluorescence revealed wide expression of KPC1 in the spinal cord, including expression in neurons and astrocytes. After injury, KPC1 expression was increased predominantly in astrocytes, which highly expressed PCNA, a marker for proliferating cells. Co-immunoprecipitation demonstrated increased interactions between p27kip1 and KPC1 4 days after injury. To understand whether KPC1 plays a role in astrocyte proliferation, we applied LPS to induce astrocyte proliferation in vitro. Western blot analysis demonstrated that p27kip1 expression was negatively correlated with KPC1 expression following LPS stimulation. Immunofluorescence analysis showed subcellular localizations of p27kip1 and KPC1 were also changed following the stimulation of astrocytes with LPS. These results suggest that KPC1 is related to the down-regulation of p27kip1; this event may be involved in the proliferation of astrocytes after SCI.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30770488, No. 30870320, No. 31070723, No. 81071487 and No. 81070275), Natural Science Foundation of Jiangsu Province (No. BK2009156, No. BK2009157 and No. BK2009161; BK2009169), the 333 high-level personnel training project of Jiangsu Province (No. BRA2010137) and the Natural Science Foundation of Zhejiang Province (Y2090545).

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Authors and Affiliations

  1. Orthopedic Department, Affiliated Hospital of Nantong University, and The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, 226001, Nantong, People’s Republic of China

    Jian Zhao, Shuangwei Zhang, Xiujie Wu, Weipeng Huan, Zhiqiang Liu, Haixiang Wei & Aiguo Shen

  2. Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical College, 325000, Wenzhou, Zhejiang, People’s Republic of China

    Honglin Teng

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  1. Jian Zhao
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  2. Shuangwei Zhang
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  3. Xiujie Wu
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  4. Weipeng Huan
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  5. Zhiqiang Liu
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  7. Aiguo Shen
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Correspondence to Aiguo Shen or Honglin Teng.

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Jian Zhao and Shuangwei Zhang contributed equally to this work.

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Zhao, J., Zhang, S., Wu, X. et al. KPC1 Expression and Essential Role After Acute Spinal Cord Injury in Adult Rat. Neurochem Res 36, 549–558 (2011). https://doi.org/10.1007/s11064-010-0377-y

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  • DOI: https://doi.org/10.1007/s11064-010-0377-y

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