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Activation of JNK/SAPK in Primary Glial Cultures: II. Differential Activation of Kinase Isoforms Corresponds to Their Differential Expression

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Abstract

Recently, we reported on the activation of c-Jun N-terminal kinase (JNK) in primary glial cells noting certain differences in the patterns of kinase activation in astrocytes and oligodendrocytes (Zhang et al., J Neurosci Res 46:114–121;1996). In this extended study, we have examined the activation and expression levels of JNK1 and JNK2 isoforms in different glial cell types including the two in vitro-defined astroglial subtypes (type-1 and type-2), oligodendrocytes and microglia. An in-gel kinase assay of cell extracts and JNK-immunoprecipitates revealed the activation of both JNK1 and JNK2 in type-1 astrocytes in response to TNFα, and in microglia, in response to TNFα and bacterial lipopolysaccharide. The strong activation of the two JNK isoforms in type-1 astrocytes and microglia contrasted with a predominant activation of JNK1 over JNK2 in type-2 astrocytes and oligodendrocytes, the two glial subtypes sharing a common lineage. Immunoblot and immunocytochemical analyses using isoform-speciflc antibodies showed a differential expression of the two isoforms in different glial cells thereby accounting for their observed differential activation.

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REFERENCES

  1. Cano, E., and Mahadevan, L. C. 1995. Parallel signal processing among mammalian MAPKs. Trends Biochem. Sci. 20:117-122.

    PubMed  Google Scholar 

  2. Kyriakis, J. M., and Avruch, J. 1996. Sounding the alarm: Protein kinase cascades activated by stress and inflammation. J. Biol. Chem. 271:24313-24316.

    PubMed  Google Scholar 

  3. Kyriakis, J. M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., and Woodgett, J. R. 1994. The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369:156-160.

    Article  PubMed  Google Scholar 

  4. Gupta, S., Barrett, T., Whitmarsh, A. J., Cavanagh, J., Sluss, H. K., Derijard, B., and Davis, R., 1996. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J. 15:2760-2770.

    PubMed  Google Scholar 

  5. Hill, C. S., and Treisman, R. 1995. Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 80:199-211.

    PubMed  Google Scholar 

  6. Karin, M. 1995. The regulation of AP-1 activity by mitogen-activated protein kinases. J. Biol. Chem. 270:16483-16486.

    PubMed  Google Scholar 

  7. Barna, B. P., Estes, M. L., Jacobs, B. S., Hudson, S., and Ransohoff, R. M. 1990. Human strocytes proliferate in response to tumor necrosis factor alpha. J. Neuro-immunol. 30:239-243.

    Google Scholar 

  8. Giulian, D., Woodward, J., Young, D. G., Krebs, J. F., Lachman, L. B. 1988. Interleukin-1 injected into mammalian brain stimulates astrogliosis and neovascularization. J. Neurosci. 8:2485-2490.

    PubMed  Google Scholar 

  9. Yong, V. W., Moumdijian, R., Young, F. P., Ruijs, T. G. C., Freedman, M. S., Cashman, N., and Antel, J. P. 1991. Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc. Natl. Acad. Sci. USA. 88:7016-7020.

    PubMed  Google Scholar 

  10. D'Souza, S., Alinauskas, K., McCrea, E., Goodyear, C., and Antel, J. P. 1995. Differential susceptibility of human CNS-derived cell populations to TNF-dependent and independent immune-mediated injury. J. Neurosci. 15:7293-7230.

    PubMed  Google Scholar 

  11. Raine, C. S. 1995. Multiple sclerosis: TNF revisited, with promise. Nature Med. 1:211-214.

    PubMed  Google Scholar 

  12. Vartanian, T., Li, Y., Zhao, M., and Stefansson, K. 1995. Interferon-γ induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis. Mol. Med. 1:732-743.

    PubMed  Google Scholar 

  13. Zhang, P., Miller, B. S., Rosenzweig, S. A., and Bhat, N. R. 1996. Activation of c-Jun N-terminal kinase/stress-activated protein kinase in primary glial cultures. J. Neurosci. Res. 46:114-121.

    PubMed  Google Scholar 

  14. Perry, V. H., Andersson, P-B., and Gordon, S. 1993. Macrophages and inflammation in the central nervous system. Trends Neurosci. 16:268-273.

    PubMed  Google Scholar 

  15. Streit, W. J., and Kincaid-Colton, C. A. 1995. The brain's immune system. Sci. Am. 273:54-61.

    PubMed  Google Scholar 

  16. Wekerle, H. 1995. Antigen presentation by central nervous system glia. Pages 685-699, In Kettenman, H., and Ransom, B. R. (eds.), Neuroglia. Oxford Univ Press.

    Google Scholar 

  17. Dickson, D. W., Mattiace, L. A., Kure, K., Hutchins, K., Lyman, W. D., Brosnan, C. F. 1991. Biology of disease: Microglia in human disease, with an emphasis on acquired immune deficiency syndrome. Lab. Invest. 64:135-156.

    PubMed  Google Scholar 

  18. Giulian, D. 1992. Microglia and disease of the nervous system. Curr. Topics Neurol. 12:23-54.

    Google Scholar 

  19. Kruetzberg, G. W. 1996. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19:312-318.

    PubMed  Google Scholar 

  20. Merrill, J. E., and Benveniste, E. N. 1996. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci. 19:331-338.

    PubMed  Google Scholar 

  21. Sweet, M. J., and Hume, D. A. 1996. Endotoxin signal transduction in macrophages. J. Leuk. Biol. 60:8-26.

    Google Scholar 

  22. Ulevitch, R. J., and Tobias, P. S. 1995. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Ann. Rev. Immunol. 13:437-457.

    Google Scholar 

  23. Bhat, N. R., Hauser, K. F., and Kindy, M. S. 1992. Cell proliferation and proto-oncogene induction in oligodendroglial progenitors. J. Neurosci. Res. 32:340-349.

    PubMed  Google Scholar 

  24. Bhat, N. R., Zhang, P., and Bhat, A. N. 1995. Expression of MARCKS in oligodendrocytes is developmentally regulated. Dev. Neurosci. 17:256-263.

    PubMed  Google Scholar 

  25. Bhat, N. R., and Zhang, P. 1994. Inhibitors of N-linked oligosaccharide processing glucosidases interfere with oligodendrocyte differentiation in culture. J. Neurosci. Res. 39:1-10.

    PubMed  Google Scholar 

  26. Hibi, M., Lin, A., Smeal, T., Minden, A., and Karin, M. 1993. Identification of an oncoprotein-and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 7:2135-2148.

    PubMed  Google Scholar 

  27. Miller, B. S., Shankavaram, U. T., Horney, M. J., Gore, A. C. S., Kurtz, D. T., and Rosenzweig, S. A. 1996. Activation of c-Jun NH2-terminal kinase/stress-activated protein kinase by insulin. Biochemistry 35:8769-8775.

    PubMed  Google Scholar 

  28. Raff, M. C., Miller, R. H., and Noble, M. 1983. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303:390-396.

    PubMed  Google Scholar 

  29. Bruce, A. J., Boling, W., Kindy, M. S., Peschon, J., Kraemer, P. J., Carpenter, M. K., Holtsberg, F. W., and Mattson, M. P. 1996. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nature Med. 7:788-794.

    Google Scholar 

  30. Hambleton, J., Weinstein, S. L., Lem, L., and DeFranco, A. L. 1996. Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages. Proc. Natl. Acad. Sci. USA. 93:2774-2778.

    PubMed  Google Scholar 

  31. Lee, J. C., and Young, P. R. 1996. Role of CSBP/p38/RK stress-response kinase in LPS and cytokine signaling mechanisms. J. Leuk. Biol. 59:152-157.

    Google Scholar 

  32. Becher, B., Federowicz, V., and Antel, J. 1996. Regulation of CD14 expression on human adult central nervous system-derived microglia. J. Neurosci. Res. 45:375-38.

    PubMed  Google Scholar 

  33. Galea, E., Reis, D. J., Fox, E. S., Xu, H., and Feinstein, D. L. 1996. CD14 mediates endotoxin induction of nitric oxide synthase in cultured brain glial cells. J. Neuro-immunol. 64:19-28.

    Google Scholar 

  34. Bhat, N. R., Lee, J. C., and Zhang, P. 1997. MAP kinase cascades and microglial activation. J. Neurochem. 69(suppl.) S206D.

    Google Scholar 

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Authors and Affiliations

  1. Departments of Neurology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC, 29425

    P. Zhang, E. L. Hogan & N. R. Bhat

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  1. P. Zhang
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  2. E. L. Hogan
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Zhang, P., Hogan, E.L. & Bhat, N.R. Activation of JNK/SAPK in Primary Glial Cultures: II. Differential Activation of Kinase Isoforms Corresponds to Their Differential Expression. Neurochem Res 23, 219–225 (1998). https://doi.org/10.1023/A:1022489127107

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