Microtubules: a Susceptible Target of Methylmercury Cytotoxicity

  • Kyoko Miura
  • Nobumasa Imura
Part of the Rochester Series on Environmental Toxicity book series (RSET)


Alteration of many kinds of cellular functions by methylmercury (MM) exposure in vitro have been reported. However, the causal mechanism for the specific dysfunction of nervous systems has not been clarified yet. We have previously demonstrated that microtubules in cultured mouse glioma cells are specifically disrupted by MM before the morphological disorders of the other organelles are detected. This specific impairment of microtubules inhibited cell growth.

In addition, we have recently found that the increased cellular pool of tubulin subunits by microtubule depolymerization with MM resulted in an inhibition of tubulin biosynthesis. Since the protein bands other than tubulin on gradient urea-PAGE gel appeared to remain unchanged under the experimental condition used, the inhibition of tubulin synthesis by MM was specific. This reduction in tubulin synthesis was well associated with the specific decline of mRNA level of β-tubulin. On the other hand, the transcription rate of tubulin gene was confirmed to be unchanged in isolated nuclei derived from MM-treated cells.

These results indicate that the growth inhibitory concentration of MM depolymerizes microtubules in mouse glioma cells and, in addition, inhibits tubulin synthesis through the autoregulatory control by the increased pool of tubulin subunits probably at the post transcriptional stages as in the case of colchicine treatment.


Neuroblastoma Cell Mercuric Chloride Inorganic Mercury Tubulin Polymerization Tubulin Dimer 
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  1. Ben Ze’ev, A., Farmer, S. R., and Penman, S., 1979, Mechanisms of regulating tubulin synthesis in cultured mammalian cells, Cell, 17:319.CrossRefGoogle Scholar
  2. Chao, E. S. E., Gierthy, J. F., Frenkel, G. D., 1984, A comparative study of the effects of mercury compounds on cell viability and nucleic acid synthesis in HeLa cells, Biochem. Pharmacol., 33:1941.PubMedCrossRefGoogle Scholar
  3. Cleveland, D. W., Pittenger, M. F., and Feramisco, J. R., 1983, Elevation of tubulin levels by microinjection suppresses new tubulin synthesis, Nature (London), 305:738.CrossRefGoogle Scholar
  4. Gruenwedel, D. W., and Cruikshank, M. K., 1979. Effect of methylmercury (II) on the synthesis of deoxyribonucleic acid, ribonucleic acid and protein in HeLa S3 cells, Biochem. Pharmacol., 28:651.Google Scholar
  5. Imura, N., Miura, K., Inokawa, M., and Nakada, S., 1980, Mechanism of methylmercury cytotoxicity: by biochemical and morphological experiments using cultured cells, Toxicology, 17:241.PubMedCrossRefGoogle Scholar
  6. Imura, N., and Miura, K., 1986, Mode of toxic action of methylmercury, in: “Recent Advances Minamata Disease Studies,” T. Tsubaki and H. Takahashi, eds., pp. 169–188, Kodansha, Tokyo.Google Scholar
  7. Miura, K., and Imura, N., 1987, Mechanism of methylmercury cytotoxicity, CRC Crit. Rev. Toxicol., 18:161.CrossRefGoogle Scholar
  8. Miura, K., and Imura, N., 1989, Mechanism of cytotoxicity of methylmercury, with special reference to microtubule disruption, Biol. Trace Element Res., 21:313.CrossRefGoogle Scholar
  9. Miura, K., Inokawa, M., and Imura, N., 1984, Effects of methylmercury and some metal ions in microtubule networks in mouse glioma cells and in vitro tubulin polymerization, Toxicol. Appl. Pharmacol., 73, 218.PubMedCrossRefGoogle Scholar
  10. Miura, K., Nakada, S., Suzuki, K., and Imura, N., 1979, Ultrastructural studies on the cytotoxic effects of mercuric chloride on mouse glioma, Ecotoxicol. Environ. Saf., 3:352.PubMedCrossRefGoogle Scholar
  11. Miura, K., Suzuki, K., and Imura, N., 1978, Effects of methylmercury on mitotic mouse glioma cells, Environ. Res., 17:453.PubMedCrossRefGoogle Scholar
  12. Nakada, S., and Imura, N., 1980, Stimulation of DNA synthesis and pyrimidine deoxyribonucleoside transport systems in mouse glioma and mouse neuroblastoma cells by inorganic mercury, Toxicol. Appl. Pharmacol., 53:24.PubMedCrossRefGoogle Scholar
  13. Nakada, S., and Imura, N., 1987, Uptake of methylmercury and inorganic mercury by mouse glioma and mouse neuroblastoma cells, Neurotoxicology, 3:249.Google Scholar
  14. Nakada, S., Nomoto, A., and Imura, N., 1980, Effect of methylmercury and inorganic mercury of protein synthesis in mammalian cells, Ecotoxicol. Environ., Saf., 4:184.CrossRefGoogle Scholar
  15. Rodier, P. M., Aschner, M., and Sager, P. R., 1984, Mitotic arrest in the developing CNS after prenatal exposure to methylmercury, Neurobehav. Toxicol. Teratol., 6:379.PubMedGoogle Scholar
  16. Sager, P. R., Doherty, R. A., and Olmsted, J. B., 1983, Interaction of methylmercury with microtubules in cultured cells and in vitro, Exp. Cell Res., 146:127.PubMedCrossRefGoogle Scholar
  17. Sager, P. R., and Syversen, T. L. M., 1984, Differential responses to methylmercury exposure and recovery in neuroblastoma and glioma cells and fibroblasts, Exp. Neurol., 85, 371.PubMedCrossRefGoogle Scholar
  18. Sarafian, T. A., Cheung, M. K., and Verity, M. A., 1984, In vitro methylmercury inhibition of protein synthesis in neonatal cerebellar perikarya, Neuropathol. Appl. Neurobiol., 10:85.PubMedCrossRefGoogle Scholar
  19. Vogel, D. G., Rabinovitch, P. S., and Mottet, N. K., 1986, Methylmercury effects on cell cycle kinetics, Cell Tissue Kinet., 19:227.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Kyoko Miura
    • 1
    • 2
  • Nobumasa Imura
    • 2
  1. 1.Department of Environmental SciencesWako UniversityMachida-shi, TokyoJapan
  2. 2.Department of Public Health, School of Pharmaceutical SciencesKitasato UniversityMinato-ku, TokyoJapan

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