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Different Functions of HIPK2 and CtBP2 in Traumatic Brain Injury

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Abstract

Traumatic brain injury (TBI) initiates a complex series of neurochemical and signaling changes that lead to neuronal dysfunction and over-reactive astrocytes. In our study, homeodomain interacting protein kinase 2 (HIPK2) can interact with C-terminal binding protein 2 (CtBP2) in rat brain, which is a component of Wnt-regulated transcription. Up to now, the functions of HIPK2 and CtBP2 in CNS are still with limited acquaintance. In our study, we found that the interaction between HIPK2 and CtBP2 was involved in central nervous system (CNS) injury and repair. We performed an acute TBI model in adult rats. Western blot and immunohistochemistry analysis revealed that both HIPK2 and CtBP2 significantly increased in the peritrauma brain cortex in comparison to contralateral cerebral cortex. And immunofluorescence double-labeling revealed that HIPK2 was mainly co-expressed with NeuN but less GFAP. Meanwhile, we also examined that the expression profiles of active-caspase-3 was correlated with the expression of HIPK2 and the expression profiles of the proliferating cell nuclear antigen (PCNA) was correlated with the expression of CtBP2. HIPK2 participated in apoptosis of neurons, but CtBP2 was associated with the activation and proliferation of astrocytes. Immunoprecipitation further showed that they enhanced the interaction with each other in the pathophysiology process. In conclusion, this was the first description that HIPK2 interacted with CtBP2 in traumatic brains. Our data suggest that HIPK2 and CtBP2 might play important roles in CNS pathophysiology after TBI, and might provide a basis for the further study on their roles in regulating the prognosis after TBI.

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Abbreviations

TBI:

Traumatic brain injury

HIPK2:

Homeodomain interacting protein kinase 2

CtBP2:

C-terminal binding protein 2

Mdm2:

Murine double minute 2

PCNA:

Proliferating cell nuclear antigen

JNK:

c-Jun NH2-terminal kinase

PVDF:

Polyvinylidine difluoride filter

CNS:

Central nervous system

SDS:

Sodium dodecyl sulfate

BSA:

Bovine serum albumin

DAB:

Diaminobenzidine

PBS:

Phosphate buffer solution

NeuN:

Neuronal nuclei

GFAP:

Glial fibrillary acidic protein

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

PAGE:

Polyacrylamide gel electrophoresis

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Authors and Affiliations

  1. Department of Neurology, Surgical Comprehensive Laboratory Affiliated Hospital of Nantong University, 19 Qi-Xiu Road, Nantong, Jiangsu Province, 226001, China

    Feihui Zou, Hongran Fu, Hui Mao, Mingjie Gong, Gang Cui, Yang Zhang, Wei Shi & Jian Chen

  2. Department of Psychiatric, Mental Health Center Affiliated Hospital of Nantong University, Nantong, China

    Jian Xu & Jianhua Cao

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  1. Feihui Zou
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  2. Jian Xu
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  3. Hongran Fu
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  4. Jianhua Cao
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  5. Hui Mao
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  9. Wei Shi
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Correspondence to Wei Shi or Jian Chen.

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Zou, F., Xu, J., Fu, H. et al. Different Functions of HIPK2 and CtBP2 in Traumatic Brain Injury. J Mol Neurosci 49, 395–408 (2013). https://doi.org/10.1007/s12031-012-9906-2

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