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A proteomic analysis of the effect of mapk pathway activation on l-glutamate-induced neuronal cell death

Abstract

Oxidative stress has been implicated in the pathogenesis of neuronal degenerative diseases. It is also widely known that oxidative stress induces mitogen-activated protein kinase (MAPK) signaling cascades. In this study, we used proteomic analysis to investigate the role of the MAPK pathway in oxidative stress-induced neuronal cell death. The results demonstrated that several proteins, including eukaryotic translation elongation factor 2 (eEF2) and enolase I, showed a differential expression pattern during the neuronal cell death process, and this was MAPK pathway dependent. Several chaperone and cytoskeletal proteins including heat shock protein 70, calreticulin, vimentin, prolyl 4-hydroxylase β polypeptide, and transgelin 2 were up-or down-regulated, despite their expressions not depending on the MAPK pathway. These findings strongly suggest that the expressions of proteins which play protective roles are independent of the MAPK pathway. On the other hand, eEF2 and enolase I may be the downstream targets of the MAPK pathway.

Abbreviations

Cy2:

3-(4-carboxymethyl) phenylmethyl-3’-ethyloxacarbocyanine halide

Cy3:

1-(5-carboxypentile)-1’-propylindocarbocyanine halide

Cy5:

1-(5-carboxypentile)-1’-methylindocarbocyanine halide

DIGE:

differential in gel electrophoresis

GSH:

glutathione

MAPK:

mitogen-activated protein kinase

MEK:

MAPK/ERK kinase

ROS:

reactive oxygen species

References

  1. 1.

    Vannucci, S. and Hagberg, H. Hypoxia-ischemia in the immature brain. J. Exp. Biol. 207 (2004) 3149–3154.

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Coyle, J.T. and Puttfarcken, P. Oxidative stress, glutamate and neurodegenerative disorders. Science 262 (1993) 689–695.

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Mattson, M.P., Duan, W., Pedersen, W.A. and Culmsee, C. Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6 (2001) 69–81.

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Behl, C., Davis, J.B., Lesley, R. and Schubert, D. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77 (1994) 817–827.

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Tan, S., Wood, M. and Maher, P. Oxidative stress induces a form of programmed cell death with characteristics of both apoptosis and necrosis in neuronal cells. J. Neurochem. 71 (1998) 95–105.

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Tan, S., Schubert, D. and Maher, P. Oxytosis: A novel from of programmed cell death. Curr. Top. Med. Chem. 1 (2001) 497–506.

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Maher, P. and David, J.B. The role of monoamine metabolism in oxidative glutamate toxicity. J. Neurosci. 16 (1996) 6394–6401.

    PubMed  CAS  Google Scholar 

  8. 8.

    Satoh, T., Nakatsuka, D., Watanabe, Y., Nagata, I., Kikuchi, H. and Namura, S. Neuroprotection by MAPK/ERK kinase inhibition with U0126 against oxidative stress in a mouse neuronal cell line and rat primary cultured cortical neurons. Neurosci. Lett. 288 (2000) 163–166.

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Stanciu, M., Wang, Y., Kentor, R., Burke, N., Watkins, S., Kress, G., Reynolds, I., Klann, E., Angiolieri, M.R., Johnson, J.W. and DeFranco, D.B. Persistent activation of ERK contributes to glutamate-induced oxidative toxicity in a neuronal cell line and primary cortical neuron cultures. J. Biol. Chem. 275 (2000) 12200–12206.

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Robinson, M.J. and Cobb, M.H. Mitogen-activated protein kinase pathways. Curr. Opin. Cell Biol. 9 (1997) 180–186.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Wilkinson, M.G. and Millar, J.B. SAPKs and transcription factors do the nucleocytoplasmic tango. Genes Dev. 12 (1998) 1391–1397.

    PubMed  CAS  Google Scholar 

  12. 12.

    Xia, Z., Dickens, M., Raingeaud, J., Davis, R.J. and Greenberg, M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270 (1995) 1326–1331.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Sgambato, V., Pages, C., Rogard, M., Besson, M.J. and Caboche, J.J. Extracellular signal-regulated kinase (ERK) controls immediate early gene induction on corticostriatal stimulation. J. Neurosci. 18 (1998) 8814–8825.

    PubMed  CAS  Google Scholar 

  14. 14.

    Stanciu, M. and DeFranco, D.B. Prolonged nuclear retention of activated extracellular signal-regulated kinase promotes cell death generated by oxidative toxicity or proteasome inhibition in a neuronal cell line. J. Biol. Chem. 277 (2002) 4010–4017.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Levinthal, D.J. and DeFranco, D.B. Transient phosphatidylinositol 3-kinase inhibition protects immature primary cortical neurons from oxidative toxicity via suppression of extracellular signal-regulated kinase activation. J. Biol. Chem. 279 (2004) 11206–11213.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Morimoto, B.H. and Koshland, D.E. Induction and expression of long and short term neurosecretory potentiation in a neural cell line. Neuron 5 (1990) 875–880.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Huber, L.A., Pfaller, K. and Vietor, I. Organelle proteomics: implications for subcellular fractionation in proteomics. Circ. Res. 16 (2003) 962–968.

    Article  CAS  Google Scholar 

  18. 18

    Levinthal, D.J. and DeFranco, D.B. Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons. J. Biol. Chem. 280 (2005) 5875–5883.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Byun, Y., Chen, F., Chang, R., Trivedi, M., Green, K.J. and Cryns, V.L. Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis. Cell Death Diff. 8 (2001) 443–450.

    Article  CAS  Google Scholar 

  20. 20.

    Davies, C.C., Mason, J., Wakelam, M.J.O., Young, L.S. and Eliopoulos, A.G. Inhibition of phosphatidylinositol 3-kinase and ERK MAPK-regulated protein synthesis reveals the pro-apoptotic properties of CD40 ligation in carcinoma cells. J. Biol. Chem. 279 (2004) 1010–1019.

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Wang, L. and Proud, C.G. Regulation of the phosphorylation of elongation factor 2 by MEK-dependent signaling in adult cardiomyocytes. FEBS Lett. 531 (2002) 285–289.

    PubMed  Article  CAS  Google Scholar 

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Correspondence to Kwang-Hee Bae.

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Kang, S., Kim, E.Y., Bahn, Y.J. et al. A proteomic analysis of the effect of mapk pathway activation on l-glutamate-induced neuronal cell death. Cell Mol Biol Lett 12, 139–147 (2007). https://doi.org/10.2478/s11658-006-0057-8

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  • DOI: https://doi.org/10.2478/s11658-006-0057-8

Key words

  • Apoptosis
  • HT22
  • MAPK
  • Oxidative stress
  • Reactive oxygen species
  • U0126