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Effect of methionine sulfoximine on methylation of guanine residues in astroglial transfer ribonucleic acids

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Abstract

Culture-grown astrocytes derived from 3-day-old rat brain were incubated in the presence of [3H]guanosine and of the convulsant agentl-methionine-dl-sulfoximine (MSO). The resulting [3H]tRNA was purified from control and MSO-exposed cells at several time points during the incubation and was hydrolyzed to [3H]guanine and four [3H]methyl guanines which were separated by high pressure liquid chromatography. Three of the four [3H]methyl guanines were more highly labeled in the [3H]tRNA of the MSO-exposed cells, relative to that of the control cells throughout the entire incubation period. The findings extend to cultured astrocytes, the stimulatory effect of MSO on the methylation of neural tRNA guanines, previouly observed both in vitro using [14C]S-adenosyl-l-methionine and in vivo using [methyl 3-H]l-methionine.

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References

  1. Sellinger, O. Z., Dainat, J., andSalas, C. E. 1977. The relationship of tRNA methylation to brain protein synthesis during cortical and cerebellar development. Pages 55–70,in Roberts S., Lajtha, A., andGispen, W. H. (eds.), Mechanisms, regulation and special functions of protein synthesis in the brain, Elsevier/North Holland Press, Amsterdam.

    Google Scholar 

  2. Cummins, C. J., Salas, C. E., andSellinger, O. Z. 1975. The homologous methylation of tRNA in rat brain. Brain Res. 96:407–412.

    Google Scholar 

  3. Elahi, E., andSellinger, O. Z. 1979. The postnatal methylation of transfer ribonucleic acid in brain: Evidence for the methylation of precursor transfer ribonucleic acid. Biochem. J. 177:381–384.

    Google Scholar 

  4. Johnson, T. C., Mathews, R. A., andChou, L. 1974. tRNA methyltransferase activity in neonatal and mature mammalian neural tissue. J. Neurochem. 23:489–496.

    Google Scholar 

  5. Dainat, J., andSellinger, O. Z. 1980. Cerebellar tRNA methyltransferases: A developmental study. Brain Res. 183:135–143.

    Google Scholar 

  6. Dainat, J., Salas, C. E., andSellinger, O. Z. 1978. Alteration of the specificity of brain tRNA methyltransferases and of the pattern of brain tRNA methylation in vivo by methionine sulfoximine. Biochem. Pharmacol. 27:2655–2658.

    Google Scholar 

  7. Sellinger, O. Z., andDer, O. 1980. The biosynthesis of transfer ribonucleic acid in the developing rat brain and in cultured glial cells. J. Neurochem. 35:1436–1445.

    Google Scholar 

  8. Cummins, C. J., andGlover, R. A. 1978. Propagation and histological characterization of a homotypic population of astrocytes derived from neonatal rat brain. J. Anat. 125:117–125.

    Google Scholar 

  9. Phelps, G. C. 1975. An ultrastructural study of methionine sulphoximine-induced glycogen accumulation in astrocytes of the mouse cerebral cortex. J. Neurocytol. 4:479–490.

    Google Scholar 

  10. Rizzuto, N., andGonatas, N. K. 1974. Ultrastructural study of the effect of methionine sulfoximine on developing and adult rat cerebral cortex. J. Neuropathol. Exp. Neurol. 33:237–250.

    Google Scholar 

  11. Lamar, C., Jr., andSellinger, O. Z. 1965. The inhibition in vivo of cerebral glutamine synthetase and glutamine transferase by the convulsant methionine sulfoximine. Biochem. Pharmacol. 14:489–506.

    Google Scholar 

  12. Norenberg, M. D., andMartinez-Hernandez, A. 1979. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161:303–310.

    Google Scholar 

  13. Jank, P., andGross, H. J. 1974. Methyl-deficient mammalian transfer RNA. II. Homologous methylation in vitro of liver tRNA from normal and ethionine-fed rats: Ethionine effect on 5-methyl cytidine synthesis in vivo. Nucleic Acids Res. 1:1259–1267.

    Google Scholar 

  14. Klagsbrun, M. 1972. The contrast between the methylation of transfer ribonucleic acid in vivo and in vitro by normal and SV40 transformed 3T3 cells. J. Biol. Chem. 247:7443–7451.

    Google Scholar 

  15. Salas, C. E., andSellinger, O. Z. 1977. Rapid, quantitative separation by high-performance liquid chromatography of methylated bases in transfer RNA. J. Chromatogr. 133:231–236.

    Google Scholar 

  16. Yang, W. K., andNovelli, G. D. 1971. Analysis of isoaccepting tRNAs in mammalian tissues and cells. Pages 44–45,in Moldave, K., andGrossman, L. (eds.), Methods in Enzymology, Vol. XX, Part C, Academic Press, New York.

    Google Scholar 

  17. Salas, C. E., Ohlsson, W. G., andSellinger, O. Z. 1977. The stimulation of cerebralN 2-methyl- andN 22 -dimethyl-guanine-specific tRNA methyltransferases by methionine sulfoximine. Biochem. Biophys. Res. Commun. 76:1107–1115.

    Google Scholar 

  18. Macdonnell, P., Huff, K., Grouse, L., andGuroff, G. 1980. Brain nucleic acids. Pages 211–240,in Kumar, S. (ed.), Biochemistry of Brain, Pergamon Press, Elmsford, New York.

    Google Scholar 

  19. Kluge, H., Hartmann, W., Zahlten, W., andRing, U. 1971. Aktivitaetsbestimmung der Purinnukleosid-Phosphorylase aus Rattenhirn durch Produktauftrennung an Kationenaustauschern. J. Chromatogr. 56:365–367.

    Google Scholar 

  20. Snyder, F. F., Cruikshank, M. K., andSeegmiller, J. E. 1978. A comparison of purine metabolism and nucleotide pools in normal and hypoxanthine-guanine phosphoribosyltransferase-deficient neuroblastoma cells. Biochim. Biophys. Acta 543:556–569.

    Google Scholar 

  21. May, R. A., andHoffee, P. 1978. Guanosine metabolism in Novikoff hepatoma cells: Isolation and characterization of guanosine resistant variants. Arch. Biochem. Biophys. 190:712–719.

    Google Scholar 

  22. Yanagihara, T. 1979. Protein and RNA synthesis and precursor uptake with isolated nerve and glial cells. J. Neurochem. 32:169–177.

    Google Scholar 

  23. Ghittoni, N. E., Ohlsson, W. G., andSellinger, O. Z. 1970. The effect of methionine on the regional and intracellular disposition of methionine sulphoximine in rat brain. J. Neurochem. 17:1057–1068.

    Google Scholar 

  24. Schatz, R. A., Harris, R., andSellinger, O. Z. 1976. The effect of methionine on the uptake, distribution and binding of the convulsant methionine sulphoximine in the rat. Neurochem. Res. 1:53–63.

    Google Scholar 

  25. Sellinger, O. Z., Azcurra, J. M., Johnson, D. E., Ohlsson, W. G., andLodin, Z. 1971. Independence of protein synthesis and drug uptake in nerve cell bodies and glial cells isolated by a new technique. Nature (London), New Biol. 230:253–256.

    Google Scholar 

  26. Berel, A., Lehr, P. R., andGayet, J. 1977. Inhibition by metyrapone of convulsions and storage of brain glycogen in mice induced by methionine sulfoximine (MSO). Brain Res. 128:193–196.

    Google Scholar 

  27. Hevor, T. K., andGayet, J. 1979. Cyclic nucleotides in the brain of mice and rats submitted to the convulsant, methionine sulfoximine. Biochem. Pharmacol. 28:3507–3512.

    Google Scholar 

  28. Brunke, K. J., Strickler, G., andLeboy, P. S. 1980. Elevated methylation capacity of selected transfer RNA methyltransferases from 9,10-dimethyl-1,2-benzanthraceneinduced rat mammary tumors. Cancer Res. 40:417–423.

    Google Scholar 

  29. Glazer, R. I., andHartman, K. E. 1980. The comparative effects of 5-azacytidine and dihydro-5-azacytidine on 4S and 5S nuclear RNA. Mol. Pharmacol. 17:250–255.

    Google Scholar 

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Sellinger, O.Z., Der, O. Effect of methionine sulfoximine on methylation of guanine residues in astroglial transfer ribonucleic acids. Neurochem Res 6, 153–162 (1981). https://doi.org/10.1007/BF00964832

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