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Concomitant Transitory Up-Regulation of X-Linked Inhibitor of Apoptosis Protein (XIAP) and the Heterogeneous Nuclear Ribonucleoprotein C1–C2 in Surviving Cells During Neuronal Apoptosis

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Abstract

Although cap-dependent translation initiation is the prevalent mode of ribosome binding to mRNAs in eukaryotes, some mRNAs exhibit the ability to bypass the requirement for the cap structure. The translation of X-chromosome-linked inhibitor of apoptosis protein (XIAP) mRNA is controlled by an internal ribosome entry site (IRES) element, which requires the interaction of the heterogeneous nuclear ribonucleoprotein C1–C2 (hnRNP-C1/C2). We analyze, at the protein level, the time course and distribution of XIAP and hnRNP-C1/C2 upon ischemia in mice or staurosporine (STP)-induced apoptosis in HT22 cells. Both ischemia and STP induced a parallel upregulation of XIAP and hnRNP-C1/C2 protein levels in the penumbra and in HT22 cells. These results suggest that the increased levels of hnRNP C1/C2 may modulate XIAP translation, probably by interacting with the XIAP-IRES. The up-regulation of hnRNP-C1/C2 may foster the synthesis of XIAP as a protective pathway by which neurons try to counteract the initial deleterious effects of apoptosis.

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References

  1. Deveraux QL, Stennicke HR, Salvesen GS et al (1999) Endogenous inhibitors of caspases. J Clin Immunol 19:388–398

    Article  PubMed  CAS  Google Scholar 

  2. Deveraux QL, Welsh K, Reed JC (2000) Purification and use of recombinant inhibitor of apoptosis proteins as caspase inhibitors. Methods Enzymol 322:154–161

    Article  PubMed  CAS  Google Scholar 

  3. Vaux DL, Silke J (2003) Mammalian mitochondrial IAP binding proteins. Biochem Biophys Res Commun 304:499–504

    Article  PubMed  CAS  Google Scholar 

  4. Xu D, Bureau Y, McIntyre DC, Nicholson DW et al (1999) Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus. J Neurosci 19:5026–5033

    PubMed  CAS  Google Scholar 

  5. Wang X, Zhu C, Wang X, Hagberg H et al (2004) X-linked inhibitor of apoptosis (XIAP) protein protects against caspase activation and tissue loss after neonatal hypoxia-ischemia. Neurobiol Dis 16:179–189

    Article  PubMed  CAS  Google Scholar 

  6. Holcik M, Korneluk RG (2000) Functional characterization of the X-linked inhibitor of apoptosis (XIAP) internal ribosome entry site element: role of La autoantigen in XIAP translation. Mol Cell Biol 20:4648–4657

    Article  PubMed  CAS  Google Scholar 

  7. Pardo OE, Lesay A, Arcaro A et al (2003) Fibroblast growth factor 2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in small cell lung cancer cells. Mol Cell Biol 23: 7600–7610

    Article  PubMed  CAS  Google Scholar 

  8. Holcik M, Gordon BW, Korneluk RG (2003) The internal ribosome entry site-mediated translation of antiapoptotic protein XIAP is modulated by the heterogeneous nuclear ribonucleoproteins C1 and C2. Mol Cell Biol 23:280–288

    Article  PubMed  CAS  Google Scholar 

  9. Baird SD, Turcotte M, Korneluk RG et al (2006) Searching for IRES. RNA 12:1755–1785

    Article  PubMed  CAS  Google Scholar 

  10. Yoon A, Peng G, Brandenburger Y et al (2006) Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Science 12:902–906

    Article  CAS  Google Scholar 

  11. Siegelin M, Touzani O, Toutain J et al (2005) Induction and redistribution of XAF1, a new antagonist of XIAP in the rat brain after transient focal ischemia. Neurobiol Dis 20:509–518

    Article  PubMed  CAS  Google Scholar 

  12. Siegelin MD, Kossatz LS, Winckler J et al (2005) Regulation of XIAP and Smac/DIABLO in the rat hippocampus following transient forebrain ischemia. Neurochem Int 46:41–51

    Article  PubMed  CAS  Google Scholar 

  13. Rami A (2003) Ischemic neuronal death in the rat hippocampus: the calpain-calpastatin-caspase hypothesis. Neurobiol Dis 13:75–88

    Article  PubMed  CAS  Google Scholar 

  14. Althaus J, Siegelin MD, Dehghani F et al (2007) The serine protease Omi/HtrA2 is involved in XIAP cleavage and in neuronal cell death following focal cerebral ischemia/reperfusion. Neurochem Int 50:172–180

    Article  PubMed  CAS  Google Scholar 

  15. Rami A, Agarwal R, Spahn A (2007) Synergetic effects of caspase 3 and mu-calpain in XIAP-breakdown upon focal cerebral ischemia. Neurochem Res 32:2072–2079

    Article  PubMed  CAS  Google Scholar 

  16. Heurteaux C, Laigle C, Blondeau N et al (2006) Alpha-linolenic acid and riluzole treatment confer cerebral protection and improve survival after focal brain ischemia. Neuroscience 137:241–251

    Article  PubMed  CAS  Google Scholar 

  17. Paxinos G, Watson GC (1986) The rat brain in stereotaxic coordinates. Academic Press, New York, NY

    Google Scholar 

  18. Scarlett JL, Sheard PW, Hughes G et al (2000) Changes in mitochondrial membrane potential during staurosporine-induced apoptosis in Jurkat cells. FEBS Lett 475:267–272

    Article  PubMed  CAS  Google Scholar 

  19. Yuste VJ, Sanchez-Lopez I, Sole C et al (2002) The prevention of the staurosporine-induced apoptosis by Bcl-X(L), but not by Bcl-2 or caspase inhibitors, allows the extensive differentiation of human neuroblastoma cells. J Neurochem 80:126–139

    Article  PubMed  CAS  Google Scholar 

  20. Koh JY, Wie MB, Gwag BJ et al (1995) Staurosporine-induced neuronal apoptosis. Exp Neurol 135:153–159

    Article  PubMed  CAS  Google Scholar 

  21. DeGracia DJ, Hu BR (2007) Irreversible translation arrest in the reperfused brain. J Cereb Blood Flow Metab 27:875–893

    PubMed  CAS  Google Scholar 

  22. Liston P, Fong WG, Kelly NL et al (2001) Identification of XAF1 as an antagonist of XIAP anti-caspase activity. Nat Cell Biol 3:128–133

    Article  PubMed  CAS  Google Scholar 

  23. Roy N, Deveraux QL, Takahashi R et al (1997) The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J 16:6914–6925

    Article  PubMed  CAS  Google Scholar 

  24. Schiavi A, Hudder A, Werner, R (1999) Connexin43 mRNA contains a functional internal ribosome entry site. FEBS Lett 464:118–122

    Article  PubMed  CAS  Google Scholar 

  25. Zhou L, Griffin JW (2003) Demyelinating neuropathies. Curr Opin Neurol 16:307–313

    Article  PubMed  Google Scholar 

  26. Hudder A, Werner R (2000) Analysis of a Charcot-Marie-Tooth disease mutation reveals an essential internal ribosome entry site element in the connexin-32 gene. J Biol Chem 275:34586–34591

    Article  PubMed  CAS  Google Scholar 

  27. Lewis SM, Holcik M (2005) IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress. Cell Death Differ 12:547–553

    Article  PubMed  CAS  Google Scholar 

  28. Lewis SM, Veyrier A, Hosszu UN et al (2007) Subcellular relocalization of a trans-acting factor regulates XIAP IRES-dependent translation. Mol Biol Cell 18:1302–1311

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Prof. J. Stehle for scientific support. We are very grateful to A. Langhagen for technical support and C. Gandin for having performed the experiments of MCAO model.

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Correspondence to A. Rami.

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Spahn, A., Blondeau, N., Heurteaux, C. et al. Concomitant Transitory Up-Regulation of X-Linked Inhibitor of Apoptosis Protein (XIAP) and the Heterogeneous Nuclear Ribonucleoprotein C1–C2 in Surviving Cells During Neuronal Apoptosis. Neurochem Res 33, 1859–1868 (2008). https://doi.org/10.1007/s11064-008-9658-0

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  • DOI: https://doi.org/10.1007/s11064-008-9658-0

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