Cellular and Molecular Neurobiology

, Volume 33, Issue 1, pp 85–97 | Cite as

Up-regulation of Che-1 Relates to Neuronal Apoptosis After Traumatic Brain Injury in Adult Rats

  • Jian Xu
  • Wei Jin
  • Xinmin Wu
  • Xiaohong Wu
  • Aihong Li
  • Kaifu Ke
  • Jianhua Cao
  • Xiaojuan Liu
  • Xiang Tan
  • Hongran Fu
  • Yilu Gao
  • Zhiwei Gao
Original Research
First Online:
Received:
Accepted:

Abstract

Che-1, a recently identified apoptosis related protein, affects the fate of various cell types when under stress. One attractive biological function of Che-1 is promoting the transcription of p53 after DNA damage; besides, it can also regulate cell cycle via interacting with retinoblastoma protein. Although previous evidence has showed its anti-apoptotic role in cancer cells, some studies point out that Che-1 might play an opposite role in central nervous system (CNS). However, the function of Che-1 in CNS is still with limited acquaintance. To investigate whether Che-1 is involved in CNS lesion, we performed a traumatic brain injury model in adult rats. Up-regulation of Che-1 was observed in the peritrauma brain cortex by performing western blotting and immunohistochemistry. Terminal deoxynucleotidyl transferase deoxy-UTP nick-end labeling and 4′,6-diamidino-2-phenylindole staining suggested that Che-1 was involved in neuronal apoptosis after brain injury. We also investigated co-localization of Che-1 and active-caspase-3 in the ipsilateral brain cortex. In addition, the expression patterns of p53, Bax and PCNA were parallel with that of Che-1. Besides this, neurotrophin receptor-interacting MAGE homolog was found to be associated with Che-1 after brain trauma. Based on our data, we suggested that Che-1 might play an important role in neuronal apoptosis following TBI; and might provide a basis for the further study on its role in regulating the expression of p53 and cell cycle re-entry in traumatic brain injury.

Keywords

Traumatic brain injury Che-1 Neuronal apoptosis Rat 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81070992) and funded by Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Nantong University graduate scientific and technological innovation projects (No. YKC12030).

References

  1. Bacalini MG, Di Lonardo D, Catizone A, Ciccarone F, Bruno T, Zampieri M, Guastafierro T, Calabrese R, Fanciulli M, Passananti C, Caiafa P, Reale A (2011) Poly(ADP-ribosyl)ation affects stabilization of Che-1 protein in response to DNA damage. DNA Repair (Amst) 10:380–389CrossRefGoogle Scholar
  2. Barbato C, Corbi N, Canu N, Fanciulli M, Serafino A, Ciotti M, Libri V, Bruno T, Amadoro G, De Angelis R, Calissano P, Passananti C (2003) Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons. Modulation during neuronal apoptosis. Mol Cell Neurosci 24:1038–1050PubMedCrossRefGoogle Scholar
  3. Becker EB, Bonni A (2004) Cell cycle regulation of neuronal apoptosis in development and disease. Prog Neurobiol 72:1–25PubMedCrossRefGoogle Scholar
  4. Bruno T, De Angelis R, De Nicola F, Barbato C, Di Padova M, Corbi N, Libri V, Benassi B, Mattei E, Chersi A, Soddu S, Floridi A, Passananti C, Fanciulli M (2002) Che-1 affects cell growth by interfering with the recruitment of HDAC1 by Rb. Cancer Cell 2:387–399PubMedCrossRefGoogle Scholar
  5. Bruno T, De Nicola F, Iezzi S, Lecis D, D’Angelo C, Di Padova M, Corbi N, Dimiziani L, Zannini L, Jekimovs C, Scarsella M, Porrello A, Chersi A, Crescenzi M, Leonetti C, Khanna KK, Soddu S, Floridi A, Passananti C, Delia D, Fanciulli M (2006) Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer Cell 10:473–486PubMedCrossRefGoogle Scholar
  6. Bruno T, Desantis A, Bossi G, Di Agostino S, Sorino C, De Nicola F, Iezzi S, Franchitto A, Benassi B, Galanti S, La Rosa F, Floridi A, Bellacosa A, Passananti C, Blandino G, Fanciulli M (2010) Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation. Cancer Cell 18:122–134PubMedCrossRefGoogle Scholar
  7. Chen AJ, D’Esposito M (2010) Traumatic brain injury: from bench to bedside [corrected] to society. Neuron 66:11–14PubMedCrossRefGoogle Scholar
  8. Chong ZZ, Li F, Maiese K (2006) Attempted cell cycle induction in post-mitotic neurons occurs in early and late apoptotic programs through Rb, E2F1, and caspase 3. Curr Neurovasc Res 3:25–39PubMedCrossRefGoogle Scholar
  9. Cregan SP, MacLaurin JG, Craig CG, Robertson GS, Nicholson DW, Park DS, Slack RS (1999) Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons. J Neurosci 19:7860–7869PubMedGoogle Scholar
  10. Dasgupta P, Padmanabhan J, Chellappan S (2006) Rb function in the apoptosis and senescence of non-neuronal and neuronal cells: role in oncogenesis. Curr Mol Med 6:719–729PubMedGoogle Scholar
  11. Di Certo MG, Corbi N, Bruno T, Iezzi S, De Nicola F, Desantis A, Ciotti MT, Mattei E, Floridi A, Fanciulli M, Passananti C (2007) NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death. J Cell Sci 120:1852–1858PubMedCrossRefGoogle Scholar
  12. 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 102:8333–8338PubMedCrossRefGoogle Scholar
  13. Di Giovanni S, Knights CD, Rao M, Yakovlev A, Beers J, Catania J, Avantaggiati ML, Faden AI (2006) The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 25:4084–4096PubMedCrossRefGoogle Scholar
  14. Floridi A, Fanciulli M (2007) Che-1: a new effector of checkpoints signaling. Cell Cycle 6:804–806PubMedCrossRefGoogle Scholar
  15. Ghajar J (2000) Traumatic brain injury. Lancet 356:923–929PubMedCrossRefGoogle Scholar
  16. Greene LA, Liu DX, Troy CM, Biswas SC (2007) Cell cycle molecules define a pathway required for neuron death in development and disease. Biochim Biophys Acta 1772:392–401PubMedCrossRefGoogle Scholar
  17. Herrup K, Busser JC (1995) The induction of multiple cell cycle events precedes target-related neuronal death. Development 121:2385–2395PubMedGoogle Scholar
  18. Holloway RG, Quill TE (2010) Treatment decisions after brain injury—tensions among quality, preference, and cost. N Engl J Med 362:1757–1759PubMedCrossRefGoogle Scholar
  19. Hulsebosch CE, DeWitt DS, Jenkins LW, Prough DS (1998) Traumatic brain injury in rats results in increased expression of Gap-43 that correlates with behavioral recovery. Neurosci Lett 255:83–86PubMedCrossRefGoogle Scholar
  20. Jurgensmeier JM, Xie Z, Deveraux Q, Ellerby L, Bredesen D, Reed JC (1998) Bax directly induces release of cytochrome c from isolated mitochondria. Proc Natl Acad Sci USA 95:4997–5002PubMedCrossRefGoogle Scholar
  21. Kan EM, Ling EA, Lu J (2012) Microenvironment changes in mild traumatic brain injury. Brain Res Bull 87:359–372PubMedCrossRefGoogle Scholar
  22. Kendall SE, Battelli C, Irwin S, Mitchell JG, Glackin CA, Verdi JM (2005) NRAGE mediates p38 activation and neural progenitor apoptosis via the bone morphogenetic protein signaling cascade. Mol Cell Biol 25:7711–7724PubMedCrossRefGoogle Scholar
  23. Li X, Yan M, Hu L, Sun L, Zhang F, Ji H, Jiang J, Wang P, Liu H, Gao Y, Tao T, He X, Cheng C, Shen A (2010) Involvement of Src-suppressed C kinase substrate in experimental autoimmune encephalomyelitis: a link between release of astrocyte proinflammatory factor and oligodendrocyte apoptosis. J Neurosci Res 88:1858–1871PubMedGoogle Scholar
  24. Liu DX, Greene LA (2001) Neuronal apoptosis at the G1/S cell cycle checkpoint. Cell Tissue Res 305:217–228PubMedCrossRefGoogle Scholar
  25. Liu Y, Wang Y, Cheng C, Chen Y, Shi S, Qin J, Xiao F, Zhou D, Lu M, Lu Q, Shen A (2010) A relationship between p27(kip1) and Skp2 after adult brain injury: implications for glial proliferation. J Neurotrauma 27:361–371PubMedCrossRefGoogle Scholar
  26. 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 (flg) following a localized cortical brain injury. J Neurosci 12:3828–3837PubMedGoogle Scholar
  27. Maas AI, Stocchetti N, Bullock R (2008) Moderate and severe traumatic brain injury in adults. Lancet Neurol 7:728–741PubMedCrossRefGoogle Scholar
  28. Martin LJ, Liu Z, Pipino J, Chestnut B, Landek MA (2009) Molecular regulation of DNA damage-induced apoptosis in neurons of cerebral cortex. Cereb Cortex 19:1273–1293PubMedCrossRefGoogle Scholar
  29. Martinou JC, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21:92–101PubMedCrossRefGoogle Scholar
  30. Miller FD, Pozniak CD, Walsh GS (2000) Neuronal life and death: an essential role for the p53 family. Cell Death Differ 7:880–888PubMedCrossRefGoogle Scholar
  31. Park E, Bell JD, Baker AJ (2008) Traumatic brain injury: can the consequences be stopped? CMAJ 178:1163–1170PubMedCrossRefGoogle Scholar
  32. Passananti C, Fanciulli M (2007) The anti-apoptotic factor Che-1/AATF links transcriptional regulation, cell cycle control, and DNA damage response. Cell Div 2:21PubMedCrossRefGoogle Scholar
  33. Plesnila N, von Baumgarten L, Retiounskaia M, Engel D, Ardeshiri A, Zimmermann R, Hoffmann F, Landshamer S, Wagner E, Culmsee C (2007) Delayed neuronal death after brain trauma involves p53-dependent inhibition of NF-kappaB transcriptional activity. Cell Death Differ 14:1529–1541PubMedCrossRefGoogle Scholar
  34. Raghupathi R, Graham DI, McIntosh TK (2000) Apoptosis after traumatic brain injury. J Neurotrauma 17:927–938PubMedCrossRefGoogle Scholar
  35. Slemmer JE, Zhu C, Landshamer S, Trabold R, Grohm J, Ardeshiri A, Wagner E, Sweeney MI, Blomgren K, Culmsee C, Weber JT, Plesnila N (2008) Causal role of apoptosis-inducing factor for neuronal cell death following traumatic brain injury. Am J Pathol 173:1795–1805PubMedCrossRefGoogle Scholar
  36. Stoica BA, Faden AI (2010) Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics 7:3–12PubMedCrossRefGoogle Scholar
  37. Stoica BA, Byrnes KR, Faden AI (2009) Cell cycle activation and CNS injury. Neurotox Res 16:221–237PubMedCrossRefGoogle Scholar
  38. Tedeschi A, Nguyen T, Puttagunta R, Gaub P, Di Giovanni S (2009) A p53-CBP/p300 transcription module is required for GAP-43 expression, axon outgrowth, and regeneration. Cell Death Differ 16:543–554PubMedCrossRefGoogle Scholar
  39. Wang L, Wang R, Herrup K (2007) E2F1 works as a cell cycle suppressor in mature neurons. J Neurosci 27:12555–12564PubMedCrossRefGoogle Scholar
  40. Wang D, Lu Q, Shao B, Cui G, Wang Y, Liu Y, Wu Q, Zhao J, Cui Z, Xu J, Yang H, Shen A, Gu X (2011) An upregulation of SIAH1 after spinal cord injury in adult rats. J Mol Neurosci 45:134–144PubMedCrossRefGoogle Scholar
  41. Wong J, Hoe NW, Zhiwei F, Ng I (2005) Apoptosis and traumatic brain injury. Neurocrit Care 3:177–182PubMedCrossRefGoogle Scholar
  42. Yang Y, Mufson EJ, Herrup K (2003) Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease. J Neurosci 23:2557–2563PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Jian Xu
    • 1
  • Wei Jin
    • 2
  • Xinmin Wu
    • 2
  • Xiaohong Wu
    • 1
  • Aihong Li
    • 2
  • Kaifu Ke
    • 2
  • Jianhua Cao
    • 1
  • Xiaojuan Liu
    • 4
  • Xiang Tan
    • 2
  • Hongran Fu
    • 2
  • Yilu Gao
    • 3
  • Zhiwei Gao
    • 2
  1. 1.Department of PsychiatryAffiliated Mental and Health Center of Nantong UniversityNantongPeople’s Republic of China
  2. 2.Department of NeurologyAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  3. 3.Department of NeurosurgeryAffiliated Hospital of Nantong UniversityNantongPeople’s Republic of China
  4. 4.Department of ImmunologyMedical College, Nantong UniversityNantongPeople’s Republic of China

Personalised recommendations