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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Deveraux QL, Stennicke HR, Salvesen GS et al (1999) Endogenous inhibitors of caspases. J Clin Immunol 19:388–398
Deveraux QL, Welsh K, Reed JC (2000) Purification and use of recombinant inhibitor of apoptosis proteins as caspase inhibitors. Methods Enzymol 322:154–161
Vaux DL, Silke J (2003) Mammalian mitochondrial IAP binding proteins. Biochem Biophys Res Commun 304:499–504
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
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
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
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
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
Baird SD, Turcotte M, Korneluk RG et al (2006) Searching for IRES. RNA 12:1755–1785
Yoon A, Peng G, Brandenburger Y et al (2006) Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Science 12:902–906
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
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
Rami A (2003) Ischemic neuronal death in the rat hippocampus: the calpain-calpastatin-caspase hypothesis. Neurobiol Dis 13:75–88
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
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
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
Paxinos G, Watson GC (1986) The rat brain in stereotaxic coordinates. Academic Press, New York, NY
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
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
Koh JY, Wie MB, Gwag BJ et al (1995) Staurosporine-induced neuronal apoptosis. Exp Neurol 135:153–159
DeGracia DJ, Hu BR (2007) Irreversible translation arrest in the reperfused brain. J Cereb Blood Flow Metab 27:875–893
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
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
Schiavi A, Hudder A, Werner, R (1999) Connexin43 mRNA contains a functional internal ribosome entry site. FEBS Lett 464:118–122
Zhou L, Griffin JW (2003) Demyelinating neuropathies. Curr Opin Neurol 16:307–313
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
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
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
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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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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