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. 1992 Sep 1;89(17):8264–8267. doi: 10.1073/pnas.89.17.8264

Growth factors and vitamin E modify neuronal glutamate toxicity.

D Schubert 1, H Kimura 1, P Maher 1
PMCID: PMC49898  PMID: 1387712

Abstract

The sympathetic nerve cell line PC-12 is killed by glutamate in a concentration-dependent manner. Although glycine and the deletion of magnesium weakly potentiate glutamate toxicity and PC-12 cells express N-methyl-D-aspartate-receptor mRNA, most toxicity is mediated by means of a mechanism independent of typical N-methyl-D-aspartate receptors. Glutamate toxicity is, however, greatly enhanced by prior exposure to nerve growth factor or basic fibroblast growth factor. Glutamate killing is blocked by epidermal growth factor and, to a lesser extent, by vitamin E. These observations show that synergistic interactions between growth factors and excitotoxic amino acids may play critical roles in the developing nervous system and that antioxidants attenuate this toxicity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Augusti-Tocco G., Sato G. Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc Natl Acad Sci U S A. 1969 Sep;64(1):311–315. doi: 10.1073/pnas.64.1.311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Choi D. W. Glutamate neurotoxicity and diseases of the nervous system. Neuron. 1988 Oct;1(8):623–634. doi: 10.1016/0896-6273(88)90162-6. [DOI] [PubMed] [Google Scholar]
  3. Cline H. T., Debski E. A., Constantine-Paton M. N-methyl-D-aspartate receptor antagonist desegregates eye-specific stripes. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4342–4345. doi: 10.1073/pnas.84.12.4342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dykens J. A., Stern A., Trenkner E. Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. J Neurochem. 1987 Oct;49(4):1222–1228. doi: 10.1111/j.1471-4159.1987.tb10014.x. [DOI] [PubMed] [Google Scholar]
  5. Finkbeiner S., Stevens C. F. Applications of quantitative measurements for assessing glutamate neurotoxicity. Proc Natl Acad Sci U S A. 1988 Jun;85(11):4071–4074. doi: 10.1073/pnas.85.11.4071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Freese A., DiFiglia M., Koroshetz W. J., Beal M. F., Martin J. B. Characterization and mechanism of glutamate neurotoxicity in primary striatal cultures. Brain Res. 1990 Jun 25;521(1-2):254–264. doi: 10.1016/0006-8993(90)91550-z. [DOI] [PubMed] [Google Scholar]
  7. Gasic G. P., Hollmann M. Molecular neurobiology of glutamate receptors. Annu Rev Physiol. 1992;54:507–536. doi: 10.1146/annurev.ph.54.030192.002451. [DOI] [PubMed] [Google Scholar]
  8. Giotta G. J., Heitzmann J., Cohn M. Properties of two temperature-sensitive Rous sarcoma virus transformed cerebellar cell lines. Brain Res. 1980 Dec 8;202(2):445–458. doi: 10.1016/0006-8993(80)90154-7. [DOI] [PubMed] [Google Scholar]
  9. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grudt T. J., Jahr C. E. Quisqualate activates N-methyl-D-aspartate receptor channels in hippocampal neurons maintained in culture. Mol Pharmacol. 1990 Apr;37(4):477–481. [PubMed] [Google Scholar]
  11. Johnson J. W., Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987 Feb 5;325(6104):529–531. doi: 10.1038/325529a0. [DOI] [PubMed] [Google Scholar]
  12. Kater S. B., Mattson M. P., Cohan C., Connor J. Calcium regulation of the neuronal growth cone. Trends Neurosci. 1988 Jul;11(7):315–321. doi: 10.1016/0166-2236(88)90094-x. [DOI] [PubMed] [Google Scholar]
  13. Kimura H., Schubert D. Schwannoma-derived growth factor promotes the neuronal differentiation and survival of PC12 cells. J Cell Biol. 1992 Feb;116(3):777–783. doi: 10.1083/jcb.116.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Large T. H., Bodary S. C., Clegg D. O., Weskamp G., Otten U., Reichardt L. F. Nerve growth factor gene expression in the developing rat brain. Science. 1986 Oct 17;234(4774):352–355. doi: 10.1126/science.3764415. [DOI] [PubMed] [Google Scholar]
  15. Manthorpe M., Fagnani R., Skaper S. D., Varon S. An automated colorimetric microassay for neuronotrophic factors. Brain Res. 1986 Mar;390(2):191–198. doi: 10.1016/s0006-8993(86)80227-x. [DOI] [PubMed] [Google Scholar]
  16. Mattson M. P., Murrain M., Guthrie P. B., Kater S. B. Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture. J Neurosci. 1989 Nov;9(11):3728–3740. doi: 10.1523/JNEUROSCI.09-11-03728.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moriyoshi K., Masu M., Ishii T., Shigemoto R., Mizuno N., Nakanishi S. Molecular cloning and characterization of the rat NMDA receptor. Nature. 1991 Nov 7;354(6348):31–37. doi: 10.1038/354031a0. [DOI] [PubMed] [Google Scholar]
  18. Mroz E. A. Possible role of carbamates in neurotoxicity and neurotransmitter inactivation. Science. 1989 Mar 24;243(4898):1615–1615. doi: 10.1126/science.2564700. [DOI] [PubMed] [Google Scholar]
  19. Murphy T. H., Miyamoto M., Sastre A., Schnaar R. L., Coyle J. T. Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress. Neuron. 1989 Jun;2(6):1547–1558. doi: 10.1016/0896-6273(89)90043-3. [DOI] [PubMed] [Google Scholar]
  20. Oppenheim R. W. Cell death during development of the nervous system. Annu Rev Neurosci. 1991;14:453–501. doi: 10.1146/annurev.ne.14.030191.002321. [DOI] [PubMed] [Google Scholar]
  21. Schramm M., Eimerl S., Costa E. Serum and depolarizing agents cause acute neurotoxicity in cultured cerebellar granule cells: role of the glutamate receptor responsive to N-methyl-D-aspartate. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1193–1197. doi: 10.1073/pnas.87.3.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schubert D. Collaborative interactions between growth factors and the extracellular matrix. Trends Cell Biol. 1992 Mar;2(3):63–66. doi: 10.1016/0962-8924(92)90057-t. [DOI] [PubMed] [Google Scholar]
  23. Schubert D., Heinemann S., Carlisle W., Tarikas H., Kimes B., Patrick J., Steinbach J. H., Culp W., Brandt B. L. Clonal cell lines from the rat central nervous system. Nature. 1974 May 17;249(454):224–227. doi: 10.1038/249224a0. [DOI] [PubMed] [Google Scholar]
  24. Schubert D., Humphreys S., Baroni C., Cohn M. In vitro differentiation of a mouse neuroblastoma. Proc Natl Acad Sci U S A. 1969 Sep;64(1):316–323. doi: 10.1073/pnas.64.1.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. VOGT M., DULBECCO R. Steps in the neoplastic transformation of hamster embryo cells by polyoma virus. Proc Natl Acad Sci U S A. 1963 Feb 15;49:171–179. doi: 10.1073/pnas.49.2.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zhang A., Cheng T. P., Altura B. M. Magnesium regulates intracellular free ionized calcium concentration and cell geometry in vascular smooth muscle cells. Biochim Biophys Acta. 1992 Feb 19;1134(1):25–29. doi: 10.1016/0167-4889(92)90024-6. [DOI] [PubMed] [Google Scholar]

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