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Involvement of Upregulated P53-Induced Death Domain Protein (PIDD) in Neuronal Apoptosis after Rat Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) initiates a series of complicated pathological events that could eventually lead to neuronal apoptosis. Recent studies indicated that p53 played a crucial role in neuronal apoptosis and regeneration following TBI. However, the detailed mechanism of p53-induced neuronal apoptosis in TBI remains largely elusive. In this study, we identified that p53-induced death domain protein (PIDD), whose transcription could be rapidly induced by p53 activation, was significantly upregulated after TBI. Western blot and immunohistochemistrical analyses revealed that the expression of PIDD was gradually increased, reached a peak at 3 days, and then decreased gradually to basal level after brain trauma. Further, double immunofluorescent analysis showed that PIDD was distributed predominantly in neurons, and the number of PIDD-positive neurons was significantly elevated in injured brain cortex. In addition, we found that PIDD was mainly distributed in active caspase-3-positive neurons, implicating a possible involvement of PIDD in the regulation of neuronal apoptosis during TBI. Finally, we showed that the expressions of p53 and Bax were altered correlatively with PIDD after brain trauma, implying that the upregulation of PIDD after TBI might be a result of p53 activation. Taken together, these findings suggested that PIDD might be an important regulator and potential therapeutic target of TBI.

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Abbreviations

PIDD:

p53-induced death domain protein

TBI:

Traumatic brain injury

CNS:

Central neural system

NeuN:

Neuronal nuclei

RAIDD:

RIP-associated Ich-1/CED homologous protein with death domain

ATM:

Ataxia–telangiectasia-mutated protein

Bax:

Bcl-2-associated X protein

GFAP:

Glial fibrillary acidic protein

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

This work was supported by a grant of the Administration of Science and Technology of Nantong (BK2012090).

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Authors and Affiliations

  1. School of Public Health, Nantong University, Nantong, People’s Republic of China

    Chunhua Wan & Junkang Jiang

  2. Department of Neurosurgery, the First Affiliated Hospital of Soochow University, No. 188, Shixin Street, Suzhou, 215006, People’s Republic of China

    Hui Mao, Jianhua Cao, Xiaohong Wu & Gang Cui

Authors
  1. Chunhua Wan
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  2. Junkang Jiang
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  3. Hui Mao
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  4. Jianhua Cao
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  5. Xiaohong Wu
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  6. Gang Cui
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Corresponding author

Correspondence to Gang Cui.

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Chunhua Wan and Junkang Jiang contribute equally to this work.

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Wan, C., Jiang, J., Mao, H. et al. Involvement of Upregulated P53-Induced Death Domain Protein (PIDD) in Neuronal Apoptosis after Rat Traumatic Brain Injury. J Mol Neurosci 51, 695–702 (2013). https://doi.org/10.1007/s12031-013-0050-4

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  • DOI: https://doi.org/10.1007/s12031-013-0050-4

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