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Hyperbaric Oxygen Enhances the Expression of Prion Protein and Heat Shock Protein 70 in a Mouse Neuroblastoma Cell Line

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Abstract

1. Cellular prion protein, PrPC, is a ubiquitous glycoprotein strongly expressed in neurons with an as yet unknown biological function. In previous studies, we demonstrated that PrPC could be regulated by heat shock stress, implying that it might be a stress-responsive protein. Hyperbaric oxygen (HBO) administration is a well-defined model for the study of oxidative stress.

2. This study investigated the effect of HBO on PrPC and Hsp 70 expression in mouse neuroblastoma cell lines (N18), assessing the expression of PrPC and Hsp 70 using RT-PCR and Western blotting. HBO administration resulted in a time- and dose-dependent increase in PrPC and Hsp70 expression in N18 cells at both mRNA and protein levels, with a concomitant upregulation of c-Jun N-terminal kinase (JNK).

3. Under HBO treatment, luciferase reporter constructs of the rat PrPC promoter, containing the heat shock element (HSE) also present in Hsp70, expressed higher luciferase activity (3- to 10-fold) than those constructs without HSE.

4. In summary, these data suggest that PrPC and Hsp 70 may be regulated by HBO, through the activation of JNK. Thus, the activated heat shock transcriptional factor 1, phosphorylated by JNK interacted with HSE in the promoter of PrPC resulted in increased gene expression. These findings are vital for future therapeutic approaches in transmissible spongiform encephalopathies and the understanding of the function of the PrPC.

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REFENCES

  • Borchelt, D. R., Scott, M., Taraboulos, A., Stahl, N., and Prusiner, S. B. (1990). Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J. Cell Biol. 110: 743-752.

    Google Scholar 

  • Bounhar, Y., Zhang, Y., Goodyear, C., and LeBlanc, A. (2001). Prion protein protects human neurons against Bax-mediated apoptosis. J. Biol. Chem. 276: 39145-39149.

    Google Scholar 

  • Brown, D. R., and Besinger, A. (1998). Prion protein expression and superoxide dismutase activity. Biochem. J. 334: 423-429.

    Google Scholar 

  • Brown, D. R., Clive, C., and Haswell, S. J. (2001). Antioxidant activity related to copper binding of native prion protein. J. Neurochem. 76: 69-76.

    Google Scholar 

  • Brown, D. R., Wong, B. S., Hafiz, F., Clive, C., Haswell, S. J., and Jones, I. M. (1999). Normal prion protein has an activity like that of superoxide dismutase. Biochem. J. 344: 1-5.

    Google Scholar 

  • Chiesa, R., Piccardo, P., Quaglio, E., Drisaldi, B., Si-Hoe, S. L., Takao, M., Ghetti, B., and Harris, D. A. (2003). Molecular distinction between pathogenic and infectious properties of the prion protein. J. Viol. 77: 7611-7622.

    Google Scholar 

  • Coffey, E. T., Smiciene, G., Hongisto, V., Cao, J., Brecht, S., Herdegen, T., and Countney, M. J. (2002). C-Jun N-terminal protein kinase (JNK) is specifically activated by stress, mediating c-Jun activation, in the presence of constitutive JNK1 activity in cerebellar neurons. J. Neurosci. 22: 4335-4345.

    Google Scholar 

  • Dennog, C., Radermacher, P., Barnett, Y. A., and Speit, G. (1999). Antioxidant status in humans after exposure to hyperbaric oxygen. Mutat. Res. 428: 83-89.

    Google Scholar 

  • Jackson, G. S., and Clarke, A. R. (2000). Mammalian prion proteins. Curr. Opin. Struct. Biol. 10: 69-74.

    Google Scholar 

  • Jamieson, D., Chance, B., Cadenas, A., and Boveris, A. (1986). The relation of free radicle production to hyperoxia. Ann. Rev. Physiol. 48: 703-719.

    Google Scholar 

  • Konishi, T., Nomoto, M., Shimizu, K., Abe, T., and Itoh, H. (1995). Dominant role of the second heat shock element in expression of the Hsp70 gene in rat liver after whole body hyperthermia. J. Biochem. 118: 1021-1029.

    Google Scholar 

  • Kretzschmar, H. A., Stowring, L. E., Westaway, D., Stubblebine, W. H., Prusiner, S. B., and DeArmond, S. J. (1986). Molecular cloning of a human prion protein cDNA. DNA 5: 315-324.

    Google Scholar 

  • Lee, K. S., Magalhaes, A. C., Zanata, S. M., Brentani, R. R., Martins, V. R., and Prado, M. A. M. (2001). Internalization of mammalian fluorescent cellular prion protein and N-terminal deletion mutants in living cells. J. Neurochem. 79: 79-87.

    Google Scholar 

  • Liu, X., Gupta, A. K., Corry, P. M., and Lee, Y. J. (1997). Hypoglycemia-induced c-Jun phosphorylation is mediated by c-Jun N-terminal Kinase 1 and Lyn Kinase in drug-resistant human breast carcinoma MCF-7/ADR cells. J. Biol. Chem. 272: 11690-11693.

    Google Scholar 

  • Martins, V. R., Graner, E., Garcia-Abreu, J., Souza, S. J., Mercadante, A. F., Veiga, S. S., Zanata, S. M., Neto, V. M., and Brentani, R. R. (1997). Complementary hydropathy identifies a cellular prion protein receptor. Nat. Med. 3: 1376-1382.

    Google Scholar 

  • Negro, A., Ballarin, C., Bertoli, A., Massimino, M. L., and Sorgato, M. C. (2001). The metabolism and imaging in live cells of the bovine prion protein in its native form or carrying single amino acid substitutions. Mol. Cell. Neurosci. 17: 521-538.

    Google Scholar 

  • Oesch, B., Westway, D., Walchi, M., McKinley, M., Kent, S., Aebersold, R., Barry, R., Tempst, P., Teplow, D., Hood, L., Prusiner, S., and Weissmann, C. (1985). A cellular gene encodes scrapie PrP 27-30 protein. Cell 40: 735-746.

    Google Scholar 

  • Park, J., and Liu, A. Y. (2001). JNK phosphorylates the HSF1 transcriptional activation domain: Role of JNK in the regulation of the heat shock response. J. Cell. Biochem. 82: 326-338.

    Google Scholar 

  • Saeki, K., Kubosaki, A., Matsumoto, Y., and Onodera, T. (1996). Identification of a promoter region in the rat prion protein gene. Biochem. Biophys. Res. Commun. 219: 47-52.

    Google Scholar 

  • Shyu, W. C., Harn, H. J., Saeki, K., Kubosaki, A., Matsumoto, Y., Onodera, T., Chen, C. J., Hsu, Y. D., and Chiang, Y. H. (2002). Molecular modulation of expression of prion protein by heat shock. Mol. Neurobiol. 26: 1-12.

    Google Scholar 

  • Shyu, W. C., Hsu, Y. D., Kao, M. C., and Tsao, W. L. (1996). Panencephalitic Creutzfeldt-Jakob disease in a Chinese family-unusual presentation with PrP codon 210 mutation and identification by PCR-SSCP. J. Neurol. Sci. 143: 176-180.

    Google Scholar 

  • Shyu, W. C., Kao, M. C., Chou, W. Y., Hsu, Y. D., and Soong, B. W. (2000). Heat shock modulates prion protein expression in human NT-2 cells. NeuroReport 11: 771-774.

    Google Scholar 

  • Speit, G., Dennog, C., Eichhorn, U., Rothfuss, A., and Kaina, B. (2000). Induction of heme oxygenase-1 and adaptive protection against the induction of DNA damage after hyperbaric oxygen treatment. Carcinogenesis 21: 1795-1799.

    Google Scholar 

  • Speit, G., Dennog, C., and Lampl, L. (1998). Biological significance of DNA damage induced by hyperbaric oxygen. Mutagenesis 13: 85-87.

    Google Scholar 

  • Stangel, K., Gunther, C., Frank, T., Lorenz, M., Meiners, S., Ropke, T., Stelter, L., Moobed, M., Baumann, G., Kloetzel, P. M., and Stangel, V. (2002). Inhibition of the ubiquitin-proteasome pathway induces differential heat shock protein response in cardiomyocytes and renders early cardiac protection. Biochem. Biophys. Res. Commun. 291: 542-549.

    Google Scholar 

  • Sumudhu, W., Perera, S., and Hooper, N. M. (2001). Ablation of the metal ion-induced endocytosis of the prion protein by disease-associated mutation of the octarepeat region. Curr. Opin. Cell. Biol. 11: 519-523.

    Google Scholar 

  • Wada, K., Miyazawa, T., Nomura, N., Tsuzuki, N., Nawashiro, H., and Shima, K. (2001). Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in Gerbil hippocampus. Neurosurgery 49: 160-167.

    Google Scholar 

  • Westaway, D., DeArmond, S. J., Cayetano-Canlas, J., Groth, D., Foster, D., Yang, S. L., Torchia, M., Carlson, G. A., and Prusiner, S. B. (1994). Degeneration of skeletal muscle, peripheral nerves and the central nervous system in transgenic mice over expression wild-type prion protein. Cell 76: 117-129.

    Google Scholar 

  • Yoon, S. O., Yun, C. H., and Chung, A. S. (2002). Dose effect of oxidative stress on signal transduction in aging. Mech. Ageing Dev. 123: 1591-1604.

    Google Scholar 

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Shyu, WC., Lin, SZ., Saeki, K. et al. Hyperbaric Oxygen Enhances the Expression of Prion Protein and Heat Shock Protein 70 in a Mouse Neuroblastoma Cell Line. Cell Mol Neurobiol 24, 257–268 (2004). https://doi.org/10.1023/B:CEMN.0000018620.41913.d2

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  • DOI: https://doi.org/10.1023/B:CEMN.0000018620.41913.d2

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