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p53 Inactivation leads to enhancement of tyrosine hydroxylase biosynthesis in brain dopaminergic neurons

  • Comparative and Ontogenic Physiology
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Abstract

In this paper we address a possibility of interaction among protein 53, members of the ERK1/2 signaling pathway, and the CREB transcription factor in regulation of activity of dopaminergic neurons. Nerve cells in the substantia nigra and zona incerta have been studied in control rats and in rats with pifithrin-alpha, a transcriptional inhibitor of p53, administered intraperitoneally. We have shown that p53 inhibition leads to an increased tyrosine hydroxylase content both in cell bodies and axon terminals. The CREB transcription factor activity is also enhanced in brain dopaminergic neurons. However, there have been observed no significant differences in phospho-ERK1/2 kinase content between cell bodies from pifithrin-alpha injected group and the control. It has been shown therefore that p53 exerts an inhibitory effect on tyrosine hydroxylase biosynthesis which may be mediated by the CREB.

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References

  1. Hermeking, H., Lengauer, C., Polyak, K., He, T.C., Zhang, L., Thiagalingam, S., Kinzler, K.W., and Vogelstein, B., 14-3-3 Sigma Is a p53-Regulated Inhibitor of G2/M Progression, Mol. Cell, 1997, vol. 1, no. 1, pp. 3–11.

    Article  PubMed  CAS  Google Scholar 

  2. Vousden, K.H. and Prives, C., Blinded by the Light: the Growing Complexity of p53, Cell, 2009, vol. 137, no. 3, pp. 413–431.

    Article  PubMed  CAS  Google Scholar 

  3. Beckerman, R. and Prives, C., Transcriptional Regulation by p53, Cold Spring Harb. Perspect. Biol., 2010, vol. 2, no. 8.

    Google Scholar 

  4. Tendler, E., Weisinger, G., Coleman, R., Diamond, E., Lischinsky, S., Kerner, H., Rotter, V., and Zinder, O., Tissue-Specific p53 Expression in the Nervous System, Mol. Brain Res., 1999, vol. 72, pp. 40–46.

    Article  PubMed  CAS  Google Scholar 

  5. Nishimura, K., Makino, S., Tanaka, Y., Kaneda, T., and Hashimoto, K., Altered Expression of p53 m-RNA in the Brain and Pituitary during Repeated Immobilization Stress: Negative Correlation with Glucocorticoid Receptor mRNA Levels, J. Neuroendocrinol., 2004, vol. 16, pp. 84–91.

    Article  PubMed  CAS  Google Scholar 

  6. Gilman, C.P., Chan, S.L., Guo, Z., Zhu, X., Greig, N., and Mattson, M.P., p53 Is Present in Synapses Where It Mediates Mitochondrial Dysfunction and Synaptic Degeneration in Response to DNA Damage, and Oxidative and Excitotoxic Insults, Neuromolec. Med., 2003, vol. 3, no. 3, pp. 159–172.

    Article  CAS  Google Scholar 

  7. Tedeschi, A. and Di Giovanni, S., The Non-Apoptotic Role of p53 in Neuronal Biology: Enlightening the Dark Side of the Moon, EMBO Rep., 2009, vol. 10, no. 6, pp. 576–583.

    Article  PubMed  CAS  Google Scholar 

  8. Amson, R., Lassalle, J.-M., Halley, H., Prieur, S., Lethrosne, F., Roperch, J.-P., Israeli, D., Gendron, M.-C., Duyckaertsi, C., Checler, F., Dausset, J., Cohen, D., Oren, M., and Telerman, A., Behavioral Alterations Associated with Apoptosis and Down-Regulation of Presenilin 1 in the Brains of p53-Deficient Mice, PNAS, 2000, vol. 97, no. 10, pp. 5346–5350.

    Article  PubMed  CAS  Google Scholar 

  9. Chernigovskaya, E.V., Taranuhin, A.G., Glazova, M.V., Yamova, L.A., and Fedorov, L.M., Apoptotic Signaling Proteins: Possible Participation in the Regulation of Vasopressin and Cathecholamines Biosynthesis in the Hypothalamus, Histochem. Cell. Biol., 2005, vol. 124, no. 6, pp. 523–533.

    Article  PubMed  CAS  Google Scholar 

  10. Wu, G.S., The Functional Interactions between the p53 and MAPK Signaling Pathways, Cancer Biol. Ther., 2004, vol. 3, no. 2, pp. 156–161.

    PubMed  CAS  Google Scholar 

  11. Singh, S., Upadhyay, A.K., Ajay, A.K., and Bhat, M.K., p53 Regulates ERK Activation in Carboplatin Induced Apoptosis in Cervical Carcinoma: a Novel Target of p53 in Apoptosis, FEBS Lett., 2007, vol. 581, no. 2, pp. 289–295.

    Article  PubMed  CAS  Google Scholar 

  12. Gulati, A.P., Yang, Y.M., Harter, D., Mukhopadhyay, A., Aggarwal, B.B., Benzil, D.L., Whysner, J., Albino, A.P., Murali, R., and Jhanwar-Uniyal, M., Mutant Human Tumor Suppressor p53 Modulates the Activation of Mitogen-Activated Protein Kinase and Nuclear Factor-KappaB, but Not c-Jun N-Terminal Kinase and Activated Protein-1, Mol. Carcinog., 2006, vol. 45, no. 1, pp. 26–31.

    Article  PubMed  CAS  Google Scholar 

  13. Kumer, S.C. and Vrana, K.E., Intricate Regulation of Tyrosine Hydroxylase Activity and Gene Expression, J. Neurochem., 1996, vol. 67, no. 2, pp. 443–462.

    Article  PubMed  CAS  Google Scholar 

  14. Shah, P., Nankova, B.B., Parab, S., and La Gamma, E.F., Short Chain Fatty Acids Induce TH Gene Expression via ERK-Dependent Phosphorylation of CREB Protein, Brain Res., 2006, vol. 1107, no. 1, pp. 13–23.

    Article  PubMed  CAS  Google Scholar 

  15. Tinti, C., Yang, C., Seo, H., Conti, B., Kim, C., Joh, T.H., and Kim, K.S., Structure/Function Relationship of the cAMP Response Element in Tyrosine Hydroxylase Gene Transcription, J. Biol. Chem., 1997, vol. 272, no. 31, pp. 19 158–19 164.

    Article  CAS  Google Scholar 

  16. DeCastro, M., Nankova, B.B., Shah, P., Patel, P., Mally, P.V., Mishra, R., and La Gamma, E.F., Short Chain Fatty Acids Regulate Tyrosine Hydroxylase Gene Expression through a cAMP-Dependent Signaling Pathway, Brain Res. Mol. Brain Res., 2005, vol. 142, no. 1, pp. 28–38.

    Article  PubMed  CAS  Google Scholar 

  17. Nagatsu, T., Levitt, M., and Udenfriend, S., Tyrosine Hydroxylase. The Initial Step in Norepinephrine Biosynthesis, J. Biol. Chem., 1964, vol. 239, pp. 2910–2917.

    PubMed  CAS  Google Scholar 

  18. Komarova, E.A. and Gudkov, A.V., Chemoprotection from p53-Dependent Apoptosis: Potential Clinical Applications of the p53 Inhibitors, Biochem. Pharmacol., 2001, vol. 62, no. 6, pp. 657–667.

    Article  PubMed  CAS  Google Scholar 

  19. Culmsee, C.A., Zhu, X., Yu, Q.-Sh., Chan, S.L., Camandola, S., Guo, Zh., Greig, N.H., and Mattson, M.P., Synthetic Inhibitor of p53 Protects Neurons against Death Induced by Ischemic and Excitotoxic Insults, and Amyloid β-Peptide, J. Neurochem., 2001, vol. 77, pp. 220–228.

    Article  PubMed  CAS  Google Scholar 

  20. Veeranna, A., Shetty, K.T., Takahashi, M., Grant, P., and Pant, H.C., Cdk5 and MAPK Are Associated with Complexes of Cytoskeletal Proteins in Rat Brain, Brain Res. Mol. Brain Res., 2000, vol. 76, no. 2, pp. 229–236.

    Article  PubMed  CAS  Google Scholar 

  21. Luboshits, G. and Benayahu, D., MS-KIF18A, a Kinesin, Is Associated with Estrogen Receptor, J. Cell Biochem., 2007, vol. 100, no. 3, pp. 693–702.

    Article  PubMed  CAS  Google Scholar 

  22. Haycock, J.W., Ahn, N.G., Cobb, M.H., and Krebs, E.G., ERK1 and ERK2, Two Microtubule-Associated Protein 2 Kinases, Mediate the Phosphorylation of Tyrosine Hydroxylase at Serine-31 in situ, Proc. Natl. Acad. Sci. USA, 1992, vol. 89, no. 6, pp. 2365–2369.

    Article  PubMed  CAS  Google Scholar 

  23. Dunkley, P.R., Bobrovskaya, L., Graham, M.E., von Nagy-Felsobuki, E.I., and Dickson, P.W., Tyrosine Hydroxylase Phosphorylation: Regulation and Consequences, J. Neurochem., 2004, vol. 91, no. 5, pp. 1025–1043.

    Article  PubMed  CAS  Google Scholar 

  24. Adams, J.P., Roberson, E.D., English, J.D., Selcher, J.C., and Sweatt, J.D., MAPK Regulation of Gene Expression in the Central Nervous System, Acta Neurobiol. Exp. (Wars.), 2000, vol. 60, no. 3, pp. 377–394.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    N. A. Dorofeeva, L. S. Nikitina, M. V. Glazova, O. D. Kirillova & E. V. Chernigovskaya

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  1. N. A. Dorofeeva
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  2. L. S. Nikitina
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  3. M. V. Glazova
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  4. O. D. Kirillova
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  5. E. V. Chernigovskaya
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Correspondence to N. A. Dorofeeva.

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Original Russian Text © N.A. Dorofeeva, L.S. Nikitina, M.V. Glazova, O.D. Kirillova, E.V. Chernigovskaya, 2013, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2013, Vol. 49, No. 2, pp. 137–143.

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Dorofeeva, N.A., Nikitina, L.S., Glazova, M.V. et al. p53 Inactivation leads to enhancement of tyrosine hydroxylase biosynthesis in brain dopaminergic neurons. J Evol Biochem Phys 49, 175–182 (2013). https://doi.org/10.1134/S0022093013020060

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  • DOI: https://doi.org/10.1134/S0022093013020060

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