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Increased Expression of TNF Receptor-Associated Factor 6 After Rat Traumatic Brain Injury

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Abstract

TRAF6 (TNF receptor-associated factor 6), a member of tumor necrosis factor receptor-associated factors family was identified as a molecule that binds to the cytoplasmic domain of CD40. TRAF6 functions as an adaptor, positively regulating the NF-κB, JNK pathway. Additionally, some studies have reported that TRAF6 is required for apoptosis within the developing CNS and regulates cell fate decisions by inducing caspase 8-dependent apoptosis. However, its distribution and function in the central nervous system (CNS) lesion are not well understood. In this study, we performed an acute traumatic brain injury model in adult rats. And we mainly examined protein expression and cellular localization of TRAF6 during rat traumatic brain injury (TBI). Western blot analysis showed TRAF6 level significantly improved at 7 days after injury, and then declined during the following days. The protein expression of TRAF6 was further analysed by immunohistochemistry. In comparison to contralateral cerebral cortex, we observed a highly significant accumulation of TRAF6 at the ipsilateral brain. Immunofluorescence double-labeling showed that TRAF6 was co-expressed with NeuN and GFAP. Besides, co-localization of TRAF6/active caspase 3 and TRAF6/proliferating cell nuclear antigen (PCNA) were detected in NeuN and GFAP, respectively. We also examined the expression profiles of proliferating cell nuclear antigen (PCNA) and active caspase 3 whose changes were correlated with the expression profiles of TRAF6. In conclusion, this is the first description of TRAF6 expression in traumatic brains. Our data suggested that TRAF6 might play important roles in CNS pathophysiology after TBI.

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Abbreviations

TRAF:

TNF receptor-associated factor

CNS:

Central nervous system

PAGE:

Polyacrylamide gel electrophoresis

ECL:

Enhanced chemiluminescence system

BSA:

Bovine serum albumin

DAB:

Diaminobenzidin

PCNA:

Proliferating cell nuclear antigen

NeuN:

Neuronal nuclei

GFAP:

Glial fibrillary acidic protein

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  • Arch RH, Gedrich RW, Thompson CB (1998) Tumor necrosis factor receptor-associated factors (TRAFs) a family of adapter proteins that regulates life and death. Genes Dev 12:2821–2830

    Article  PubMed  CAS  Google Scholar 

  • Barnes PJ, Karin M (1997) Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071

    Article  PubMed  CAS  Google Scholar 

  • Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (1996) TRAF6 is a signal transducer for interleukin-1. Nature 383:443–446

    Article  PubMed  CAS  Google Scholar 

  • Chung JY, Park YC, Ye H, Wu H (2002) All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci 115:679–688

    PubMed  CAS  Google Scholar 

  • Deng L, Wang C, Spencer E, Yang L, Braun A, You J (2000) Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103:351–361

    Article  PubMed  CAS  Google Scholar 

  • Di Giovanni S, Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, Faden AI (2005) Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci USA 102:8333–8338

    Article  PubMed  CAS  Google Scholar 

  • Ea CK, Sun L, Inoue J, Chen ZJ (2004) TIFA activates IkappaB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6. Proc Natl Acad Sci USA 101:15318–15323

    Article  PubMed  CAS  Google Scholar 

  • Erhardt L (1996) Biochemical markers in acute myocardial infarction—the beginning of a new era. Eur Heart J 17:1781–1782

    PubMed  CAS  Google Scholar 

  • Fawcett JW (1997) Astrocytic and neuronal factors affecting axon regeneration in the damaged central nervous system. Cell Tissue Res 290:371–377

    Article  PubMed  CAS  Google Scholar 

  • Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49:377–391

    Article  PubMed  CAS  Google Scholar 

  • He L, Wu X, Siegel R, Lipsky PE (2006) TRAF6 regulates cell fate decisions by inducing caspase 8-dependent apoptosis and the activation of NF-kappaB. J Biol Chem 281:11235–11249

    Article  PubMed  CAS  Google Scholar 

  • Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG (2007) Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation. J Biol Chem 282:4102–4112

    Article  PubMed  CAS  Google Scholar 

  • Lamothe B, Campos AD, Webster WK, Gopinathan A, Hur L, Darnay BG (2008) The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL. J Biol Chem 283:24871–24880

    Article  PubMed  CAS  Google Scholar 

  • Logan A, Frautschy SA, Gonzalez AM, Baird A (1992) A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors following a localized cortical brain injury. J Neurosci 12:3828–3837

    PubMed  CAS  Google Scholar 

  • Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13:1015–1024

    Article  PubMed  CAS  Google Scholar 

  • Lomaga MA, Henderson JT, Elia AJ, Robertson J, Noyce RS, Yeh WC, Mak TW (2000) Tumor necrosis factor receptor-associated factor 6 (TRAF6) deficiency results in exencephaly and is required for apoptosis within the developing CNS. J Neurosci 20:7384–7393

    PubMed  CAS  Google Scholar 

  • McGraw J, Hiebert GW, Steeves JD (2001) Modulating astrogliosis after neurotrauma. J Neurosci Res 63:109–115

    Article  PubMed  CAS  Google Scholar 

  • Morlon A, Munnich A, Smahi A (2005) TAB 2, TRAF6 and TAK1 are involved in NF-kappaB activation induced by the TNF-receptor, Edar and its adaptator Edaradd. Hum Mol Genet 14:3751–3757

    Article  PubMed  CAS  Google Scholar 

  • Morris GF, Mathews MB (1989) Regulation of proliferating cell nuclear antigen during the cell cycle. J Biol Chem 264:13856–13864

    PubMed  CAS  Google Scholar 

  • Muroi M, Tanamoto K (2008) TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB. J Leukoc Biol 83:702–707

    Article  PubMed  CAS  Google Scholar 

  • Pollet I, Opina CJ, Zimmerman C, Leong KG, Wong F, Karsan A (2003) Bacterial lipopolysaccharide directly induces angiogenesis through TRAF6-mediated activation of NF-kappaB and c-Jun N-terminal kinase. Blood 102:1740–1742

    Article  PubMed  CAS  Google Scholar 

  • Raghupathi R (2004) Cell death mechanisms following traumatic brain injury. Brain Pathol 14:215–222

    Article  PubMed  Google Scholar 

  • Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G (2003) CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature 424:793–796

    Article  PubMed  CAS  Google Scholar 

  • Wong F, Hull C, Zhande R, Law J, Karsan A (2004) Lipopolysaccharide initiates a TRAF6-mediated endothelial survival signal. Blood 103:4520–4526

    Article  PubMed  CAS  Google Scholar 

  • Yang K, Mu XS, Hayes RL (1995) Increased cortical nuclear factor-kappa B (NF-kappa B) DNA binding activity after traumatic brain injury in rats. Neurosci Lett 197:101–104

    Article  PubMed  CAS  Google Scholar 

  • Yu TS, Zhang G, Liebl DJ, Kernie SG (2008) Traumatic brain injury-induced hippocampal neurogenesis requires activation of early nestin-expressing progenitors. J Neurosci 28:12901–12912

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Chinese 973 program (2011CS910600); the National Natural Science Foundation of China (No. 30770488, No. 30870320, No. 31070723, and No. 81070275); Natural Science Foundation of Jiangsu province (No. BK2009156, No. BK2009157, and No. BK2009161); Natural science Foundation of Jiangsu Colleges and Universities Grant (09KJB320011).

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Authors and Affiliations

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

    Jian Chen, Xiujie Wu, Wei Zhao, Wei Shi, Shuangwei Zhang, Lanchun Ni & Aiguo Shen

  2. Department of Neurosurgery, Affiliated Dongtai Hospital of Nantong University, Yancheng, 224200, Jiangsu, People’s Republic of China

    Bai Shao

Authors
  1. Jian Chen
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  2. Xiujie Wu
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  3. Bai Shao
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  4. Wei Zhao
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  5. Wei Shi
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  6. Shuangwei Zhang
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  7. Lanchun Ni
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  8. Aiguo Shen
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Correspondence to Jian Chen or Aiguo Shen.

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Jian Chen and Xiujie Wu have contributed equally to this work.

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Chen, J., Wu, X., Shao, B. et al. Increased Expression of TNF Receptor-Associated Factor 6 After Rat Traumatic Brain Injury. Cell Mol Neurobiol 31, 269–275 (2011). https://doi.org/10.1007/s10571-010-9617-6

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  • DOI: https://doi.org/10.1007/s10571-010-9617-6

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