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Cyclic AMP Response Element Modulator-1 (CREM-1) Involves in Neuronal Apoptosis after Traumatic Brain Injury

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Abstract

The cyclic AMP response element-binding protein (CREB) family can regulate biological functions of various types of cells by forming homo- or heterodimers to bind the target DNA sequences; it plays an essential role in individual neuronal function and entire neuronal circuits. One attractive activity of the CREB family is regulating the transcription of apoptosis-suppressor gene bcl-2. Cyclic AMP response element modulator-1 (CREM-1) is one member of the family with limited acquaintance. To investigate whether CREM-1 is involved in central nervous system injury and repair, we performed an acute traumatic brain injury (TBI) model in adult rats. Western blot analysis and immunohistochemistry showed a significant upregulation of CREM-1 in ipsilateral peritrauma cortex. Immunofluorescent labeling indicated that CREM-1 was localized mainly in the nuclei of neurons; co-localization of CREM-1 and active-caspase-3 in the ipsilateral cortex suggested that CREM-1 might participate in neuronal apoptosis. To further investigate the function of CREM-1, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of CREM-1 with p-CREB on PC12 cells by Western blot, immunofluorescent labeling, and co-immunoprecipitation. The result implied that the association of CREM-1 with p-CREB was enhanced in apoptotic cells. Additionally, knocking CREM-1 down with siRNA demonstrated the probable pro-apoptotic role played by CREM-1 in neuronal apoptosis. Together with our data, we hypothesized that CREM-1 might play an important role in regulating neuronal death after TBI by interacting with CREB.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81070992) and funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Nantong University graduate scientific and technological innovation projects.

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Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China, 226001

    Xinmin Wu, Wei Jin, Hongran Fu, Peipei Gong, Gang Cui, Yaohui Ni, Kaifu Ke & Zhiwei Gao

  2. Department of immunology, Medical College, Nantong University, Nantong, Jiangsu Province, People’s Republic of China, 226001

    Xiaojuan Liu

  3. Department of Psychiatry, the Fourth People’s Hospital of Nantong, Nantong, Jiangsu Province, People’s Republic of China, 226001

    Jian Xu

  4. Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China, 226001

    Yilu Gao

Authors
  1. Xinmin Wu
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  2. Wei Jin
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  3. Xiaojuan Liu
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  4. Hongran Fu
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  5. Peipei Gong
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  6. Jian Xu
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  7. Gang Cui
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  8. Yaohui Ni
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  9. Kaifu Ke
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  10. Zhiwei Gao
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  11. Yilu Gao
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Corresponding authors

Correspondence to Zhiwei Gao or Yilu Gao.

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Xinmin Wu and Wei Jin contributed equally to this work.

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Wu, X., Jin, W., Liu, X. et al. Cyclic AMP Response Element Modulator-1 (CREM-1) Involves in Neuronal Apoptosis after Traumatic Brain Injury. J Mol Neurosci 47, 357–367 (2012). https://doi.org/10.1007/s12031-012-9761-1

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  • DOI: https://doi.org/10.1007/s12031-012-9761-1

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