Effects of lead exposure on alpha-synuclein and p53 transcription

DOI: 10.4236/jbise.2009.22016   PDF   HTML     6,047 Downloads   10,298 Views  

Abstract

Objective: Epidemiological studies have found that lead exposure increases the risk for Park-inson’s disease and patients with Parkinson’s disease have lower odds of developing non-smoking-related cancer (1). It would be inter-esting therefore to find the molecular links be-tween Parkinson’s disease and cancer. To do this, we studied mRNA expression of alpha-synuclein gene, a promising genetic marker for Parkinson’s disease, and expression of the tu-mor suppressor gene p53 after oxidative stress induced by lead. Methods: We used ATDC5 cell line as a model of tumor and treated by lead nitrate for 0, 2, 4, 16, 24 and 48 hours. The mRNAs of alpha-synuclein and p53 were quan-tified by reverse transcriptase polymerase chain reaction and expressed as mean (±SD) for 3 samples at each time point. Results: Ex-pression of both of alpha-synuclein and p53 mRNA increased with increasing exposure of lead treatment. The levels of alpha-synuclein and p53 mRNA were correlated with each other (r=0.9830; P<0.001). Conclusion: We propose that lead’s neurotoxicity in PD is caused by al-pha-synuclein expression and aggregation, which releases the inhibitory influence of al-pha-synuclein on p53 expression, thereby al-lowing p53 to act as the cell’s guardian of the genome and reduce tumorigenic potential. Treatments that reduce alpha-synuclein aggre-gation may need to account for a concomitant reduction in p53’s protective effect.

Share and Cite:

Zuo, P. and Rabie, A. (2009) Effects of lead exposure on alpha-synuclein and p53 transcription. Journal of Biomedical Science and Engineering, 2, 86-89. doi: 10.4236/jbise.2009.22016.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] A. B. West, V. L. Dawson and T. M. Dawson, (2005) Trends Neurosci 28, 348-352.
[2] O. M. El-Agnaf, S. A. Salem, K. E. Paleologou, M. D. Curran, M. J. Gibson, J. A. Court, M. G. Schlossmacher and D. Allsop, (2006) FASEB J 20, 419-425.
[3] S. D. Tyner, S. Venkatachalam, J. Choi, S. Jones, N. Ghebrani-ous, H. Igelmann, X. Lu, G. Soron, B.Cooper, C. Brayton, S. Hee Park, T.Thompson, G. Karsenty, A. Bradley, and L. A. Donehower, (2002) Nature 415, 45-53.
[4] S. Coon, A. Stark, E. Peterson, A. Gloi, G. Kortsha, J. Pounds, D. Chettle and J. Gorell, (2006) Environ Health Perspect 114, 1872-1876.
[5] A. G. Osman, I. A. Mekkawy, J. Verreth, S. Wuertz, W. Kloas, and F. Kirschbaum, (2008) Environ Toxicol.
[6] J. Xu, L. D. Ji and L. H. Xu, (2006) Toxicol Lett 166, 160-167.
[7] T. Atsumi, Y. Miwa, K. Kimata and Y. Ikawa, (1990) Cell Differ Dev 30, 109-116.
[8] C. Shukunami, C. Shigeno, T. Atsumi, K. Ishizeki, F. Suzuki and Y. Hiraki, (1996) J Cell Biol 133, 457-468.
[9] P. Jenner and C. W. Olanow, (1998) Ann Neurol 44, S72-84.
[10] W. Zhou and C. R. Freed, (2004) J Biol Chem 279, 10128-10135.
[11] W. Qu, B. A. Diwan, J. Liu, R. A. Goyer, T. Dawson, J. L. Hor-ton, M. G. Cherian and M. P. Waalkes, (2002) Am J Pathol 160, 1047-1056.
[12] L. D. White, D. A. Cory-Slechta, M. E. Gilbert, E. Tiffany-Castiglioni, N. H. Zawia, M. Virgolini, A. Rossi-George, S. M. Lasley, Y. C. Qian and M. R. Basha, (2007) Toxicol Appl Phar-macol 225, 1-27.
[13] S. Bates, A. C. Phillips, P. A. Clark, F. Stott, G. Peters, R. L. Ludwig and K. H. Vousden, (1998) Nature 395, 124-125.
[14] J. Loikkanen, K. Chvalova, J. Naarala, K. H. Vahakangas and K. M. Savolainen, (2003) Toxicol Lett 144, 235-246.
[15] C. Alves Da Costa, E. Paitel, B. Vincent and F. Checler, (2002) J Biol Chem 277, 50980-50984.
[16] H. Fu and P. Boffetta, (1995) Occup Environ Med 52, 73-81.
[17] O. Wong and F. Harris, (2000) Am J Ind Med 38, 255-270.
[18] J. Wesierska-Gadek and G.Schmid, (2005) Cell Mol Biol Lett 10, 439-453

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.