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Inhibition of Na+,K+-ATPase Activity in Hippocampus of Rats Subjected to Acute Administration of Homocysteine Is Prevented by Vitamins E and C Treatment

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Abstract

In the present study we evaluated the effect of acute homocysteine (Hcy) administration on Na+,K+-ATPase activity, as well as on some parameters of oxidative stress such as total radical-trapping antioxidant potential (TRAP) and on activities of antioxidant enzymes catalase (CAT), superoxide dismutase and glutathione peroxidase in rat hippocampus. Results showed that Hcy significantly decreased TRAP, Na+,K+-ATPase and CAT activities, without affecting the activities of superoxide dismutase and glutathione peroxidase. We also verified the effect of chronic pretreatment with vitamins E and C on the reduction of TRAP, Na+,K+-ATPase and CAT activities caused by Hcy. Vitamins E and C per se did not alter these parameters, but prevented the reduction of TRAP, Na+,K+-ATPase and CAT activities caused by Hcy. Our results indicate that oxidative stress is probably involved in the pathogenesis of homocystinuria and that reduction of Na+,K+-ATPase activity may be related to the neuronal dysfunction found in homocystinuric patients.

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REFERENCES

  1. Mudd, S. H., Levy, H. L., and Skovby, F. 2001. Disorders of transsulfuration. Pages 1279–1327, in Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D. (eds). The metabolic and molecular bases of inherited disease, 8th ed. McGraw-Hill, New York.

    Google Scholar 

  2. Erecinska, M. and Silver, I. A. 1994. Ions and energy in mammalian brain. Prog. Neurobiol. 16:37–71.

    Google Scholar 

  3. Lees, G. J. 1993. Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience 54:287–322.

    Google Scholar 

  4. Wyse, A. T. S., Streck, E. L., Worm, P., Wajner, A., Ritter, F., and Netto, C. A. 2000. Preconditioning prevents the inhibition of Na+,K+-ATPase activity after brain ischemia. Neurochem. Res. 25:969–973.

    Google Scholar 

  5. Grisar, T. 1984. Glial and neuronal Na+-K+ pump in epilepsy. Ann. Neurol. 16 (Suppl):128–134.

    Google Scholar 

  6. Halliwell, B. and Gutteridge, J. M. C. 1985. Oxygen radicals in the nervous system. Trends Neurosci. 8:22–26.

    Google Scholar 

  7. Welch, G. N., Upchurch, G. R., and Loscalzo, J. 1997. Homocysteine, oxidative stress and vascular disease. Hosp. Pract. 32:81–92.

    Google Scholar 

  8. Hogg, N. 1999. The effect of cyst(e)ine on the auto-oxidation of homocysteine. Free Radical Biol. Med. 27:28–33.

    Google Scholar 

  9. Kubová, H., Folbergrová, J., and Mares, P. 1995. Seizures induced by homocysteine in rats during ontogenesis. Epilepsia 36:750–756.

    Google Scholar 

  10. Streck, E. L., Zugno, A. I., Tagliari, B., Franzon, R., Wannamacher, C. M. D., Wajner, M., and Wyse, A. T. S. 2001. Inhibition of rat brain Na+,K+-ATPase activity induced by homocysteine is probably mediated by oxidative stress. Neurochem. Res. 26:1195–1200.

    Google Scholar 

  11. Fighera, M. R., Queiroz, C. M., Stracke, M. P., Brauer, M. L. N., González-Rodrigues, L. L., Frussa-Filho, R., Wajner, M., and Mello, C. F. 1999. Ascorbic acid and β-tocopherol attenuate methylmalonic acid-induced convulsions. NeuroReport 10:2039–2043.

    Google Scholar 

  12. Jones, D. H. and Matus, A. I. 1974. Isolation of plasma synaptic membrane from brain by combination flotation-sedimentation density gradient centrifugation. Biochim. Biophys. Acta 356:276–287.

    Google Scholar 

  13. Tsakiris, S. and Deliconstantinos, G. 1984. Influence of phosphatidylserine on (Na+ + K+)-stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes. Biochem. J. 22:301–307.

    Google Scholar 

  14. Chan, K. M., Delfer, D., and Junger, K. D. 1986. A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal. Biochem. 157:375–380.

    Google Scholar 

  15. Lissi, E., Pascual, C., and del Castillo, M. D. 1992. Luminol luminescence induced by 2,29'-azo-bis(2–amidopropane) thermolysis. Free Rad. Res. Comm. 17:299–311.

    Google Scholar 

  16. Aebi, H. 1984. Catalase in vitro. Methods Enzymol. 105:121–126.

    Google Scholar 

  17. Wendel, A. 1981. Glutathione peroxidase. Methods Enzymol. 77:325–332.

    Google Scholar 

  18. Lowry, O. K., Rosenbrough, R. L., Farr, R. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  19. Fuchs, D., Jaeger, M., Widner, B., Wirleitner, B., Artner-Dworzak, E., and Leblhuber, F. 2001. Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake? Clin. Chem. Lab. Med. 39:691–694.

    Google Scholar 

  20. Ames, B. N., Shigenaga, M. K., and Hagen, T. M. 1993. Oxidants, antioxidants and the degenerative diseases of aging. Proc. Natl. Acad. Sci. U.S.A. 90:7915–7922.

    Google Scholar 

  21. Jacobsen, D. J. 2000. Hyperhomocysteinemia and oxidative stress. Time for a reality check? Arterioscler. Thromb. Vasc. Biol. 20:1182–1184.

    Google Scholar 

  22. Malinow, M. R. 1990. Hyperhomocyst(e)inemia. A common and easily reversible risk factor for occlusive atherosclerosis. Circulation 81:2004–2006.

    Google Scholar 

  23. Hitschke, K., Buhler, R., Apell, H. J., and Stark G. 1994. Inactivation of the Na,K-ATPase by radiation-induced free radicals. Evidence for a radical-chain mechanism. FEBS Lett. 353:297–300.

    Google Scholar 

  24. Burton, G. W., Wronska, U., Stone, L., Foster, D. O., and Ingold, K. U. 1990. Biokinetics of dietary RRR-β-tocopherol in the male guinea-pig at three dietary levels of vitamin C and two levels of vitamin E. Lipids 25:199–210.

    Google Scholar 

  25. McCay, P. B. 1985. Vitamin E: interactions with free radical and ascorbate. Annu. Rev. Nutr. 5:323–340.

    Google Scholar 

  26. Frei, B., Stocker, R., England, L., and Ames, B. N. 1990. Ascorbate: the most effective antioxidant in the blood. Adv. Exp. Med. Biol. 264:155–163.

    Google Scholar 

  27. Carr, A. and Frei, B. 1999. Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J. 13:1007–1024.

    Google Scholar 

  28. Hara, H., Kato, H., and Kogure, K. 1990. Protective effect of alpha-tocopherol on ischemic neuronal damage in the gerbil hippocampus. Brain Res. 510:335–338.

    Google Scholar 

  29. Anderson, D. K., Waters, T. R., and Means, E. D. 1988. Pretreatment with alpha-tocopherol enhances neurologic recovery after experimental spinal cord compression injury. J. Neurotrauma 5:61–67.

    Google Scholar 

  30. Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, S., Grundman, M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., Schneider, L. S., and Thal, L. J. 1997. A controlled trial of selegiline, β-tocopherol, or both as treatment for Alzheimer' disease. N. Engl. J. Med. 336:1216–1222.

    Google Scholar 

  31. Allen, I. C., Grieve, A., and Griffiths, R. 1986. Differential changes in the content of amino acid neurotransmitters in discrete regions of the rat brain prior to the onset and during the course of homocysteine-induced seizures. J. Neurochem. 46:1582–1592.

    Google Scholar 

  32. Kim, W.-K. and Pae, Y.-S. 1996. Involvement of N-methyl-D-aspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci. Lett. 216:17–120.

    Google Scholar 

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Authors and Affiliations

  1. Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Angela T. S. Wyse, Alexandra I. Zugno, Emilio L. Streck, Cristiane Matté, Thiago Calcagnotto, Clovis M. D. Wannmacher & Moacir Wajner

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  1. Angela T. S. Wyse
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  2. Alexandra I. Zugno
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  3. Emilio L. Streck
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Wyse, A.T.S., Zugno, A.I., Streck, E.L. et al. Inhibition of Na+,K+-ATPase Activity in Hippocampus of Rats Subjected to Acute Administration of Homocysteine Is Prevented by Vitamins E and C Treatment. Neurochem Res 27, 1685–1689 (2002). https://doi.org/10.1023/A:1021647329937

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