Abstract
The objective of the present study was to investigate the effects of preincubation of hippocampus homogenates in the presence of homocysteine or methionine on Na+, K+-ATPase and Mg2+-ATPase activities in synaptic membranes of rats. Homocysteine significantly inhibited Na+, K+-ATPase activity, whereas methionine had no effect. Mg2+-ATPase activity was not altered by the metabolites. We also evaluated the effect of incubating glutathione, cysteine, dithiothreitol, trolox, superoxide dismutase and GM1 ganglioside alone or incubation with homocysteine on Na+, K+-ATPase activity. Tested compounds did not alter Na+, K+-ATPase and Mg2+-ATPase activities, but except for trolox, prevented the inhibitory effect of homocysteine on Na+, K+-ATPase activity. These results suggest that inhibition of this enzyme activity by homocysteine is possibly mediated by free radicals and may contribute to the neurological dysfunction found in homocystinuric patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
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 Basis of Inherited Disease, 8th ed., McGraw-Hill, New York.
Malinow, M. R. 1990. Hyperhomocyst(e)inemia. A common and easily reversible risk factor for occlusive atherosclerosis. Circulation 81:2004–2006.
McIlwain, H. and Poll, J. D. 1985. Interation between adenosine generated endogenously in neocortical tissues, and homocysteine and its thiolactone. Neurochem. Int. 7:103–105.
Kubová, H., Folbergrová, J., and Mares, P., 1995. Seizures induced by homocysteine in rats during ontogenesis. Epilepsia 36:750–756.
Kim, W.-K. and Pae, Y.-S., 1996. Involvement of N-Methyl-Daspartate receptor and free radical in homocysteine-mediated toxicity on rat cerebellar granule cells in culture. Neurosci. Lett. 216:117–120.
Welch, G. N., Upchurch, G. R., and Loscalzo, J., 1997. Homocysteine, oxidative stress, and vascular disease. Hosp. Pract. 32:81–92.
Hogg, N. 1999. The effect of cyst(e)ine on the auto-oxidation of homocysteine. Free Radic. Biol. Med. 27:28–33.
Erecinska, M. and Silver, I. A., 1994. Ions and energy in mammalian brain. Prog. Neurobiol. 43:37–71.
Lees, G. J., 1993. Contributory mechanisms in the causation of neurodegenerative disorders. Neuroscience 54:287–322.
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.
Grisar, T., 1984. Glial and neuronal Na+-K+ pump in epilepsy. Ann. Neurol. 16(Suppl):128–134.
Avrova, N. F., Victorov, I. V., Tyurin, V. A., Zakharova, I. O., Sokolova, T. V., Andreeva, N. A., Stelmaschuk, E. V., Tyurina, Y. Y., and Gonchar, V. S., 1998. Inhibition of glutamateinduced intensification of free radical reactions by gangliosides: possible role in their protective effect in rat cerebellar granule cells and brain synaptosomes. Neurochem. Res. 23:945–952.
Stanimirovic, D. B., Wong, J., Ball, R., and Durkin J. P., 1995. Free radical-induced endothelial membrane dysfunction at the site of blood-brain barrier: relationship between lipid peroxidation, Na,K-ATPase activity, and 51Cr release. Neurochem. Res. 20:1417–1427.
Jones, D. H. and Matus, A. I., 1974. Isolation of synaptic plasma membrane from brain by combined flotation-sedimentation density gradient centrifugation. Biochim. Biophys. Acta 356:276–287.
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.
Chan, K. M., Delfert, D., and Junger, K. D., 1986. A direct colorimetric assay for Ca2+-stimulated ATPase activity. Anal. Biochem. 157:375–380.
Bradford, M. M., 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–254.
Bergendi, L., Benes, L., Durackova, Z., and Ferencik, M., 1999. Chemistry, physiology and pathology of free radicals. Life Sci. 65:1865–1874.
Mishra, O. P., Delivoria-Papadopoulos, M., Cahillane, G., and Wagerle, L. C., 1989. Lipid peroxidation as the mechanism of modification of the affinity of the Na+, K+-ATPase active sites for ATP, K+, Na+, and strophanthidin in vitro. Neurochem. Res. 14:845–851.
Viani, P., Cervato, G., Fiorilli, A., and Cestaro, B., 1991. Agerelated differences in synaptosomal peroxidative damage and membrane properties. J. Neurochem. 56:253–258.
Yufu, K., Itoh, T., Edamatsu, R., Mori, A., and Hirakawa, M., 1993. Effect of hyperbaric oxygenation on the Na+, K(+)-ATPase and membrane fluidity of cerebrocortical membranes after experimental subarachnoid hemorrhage. Neurochem. Res. 16:1033–1039.
Meister, A. and Anderson, M. E., 1983. Glutathione. Annu. Rev. Biochem. 52:711–760.
Kraus, J. P., 1998. Biochemistry and molecular genetics of cystathionine beta-synthase deficiency. Eur. J. Pediatr. 157:50–53.
Cleland, W. W., 1964. Dithiothreitol, a new protective reagent for SH groups. Biochemistry 3:480–485.
Burton, G. W., Wronska, U., Stone, L., Foster, D. O., and Ingold, K. U. 1990. Biokinetics of dietary RRR-α-tocopherol in the male guinea-pig at three dietary levels of vitamin C and two levels of vitamin E. Lipids 25:199–210.
Hicks, D., Heidinger, V., Mohand-Said, S., Sahel, J., and Dreyfus, H., 1998. Growth factors and gangliosides as neuroprotective agents in excitotoxicity and ischemia. Gen. Pharmacol. 30:265–273.
Henneberry, R. L., Novelli, A., Cox, J. A., and Lysko, P. G., 1989. Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised neurons. An hypothesis for cell death in aging and disease. Ann. NY Acad. Sci. 568:225–233.
Renkawek, K., Renier, W. O., de Pont, J. J., Vogels, O. J., and Gabreels, F. J., 1992. Neonatal status convulsivus, spongiform encephalopathy, and low activity of Na+/K(+)-ATPase in the brain. Epilepsy 33:58–64.
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Streck, E.L., Zugno, A.I., Tagliari, B. et al. Inhibition of Rat Brain Na+, K+-ATPase Activity Induced by Homocysteine Is Probably Mediated by Oxidative Stress. Neurochem Res 26, 1195–1200 (2001). https://doi.org/10.1023/A:1013907104585
Issue Date:
DOI: https://doi.org/10.1023/A:1013907104585