Neurochemical Research

, Volume 19, Issue 7, pp 833–837 | Cite as

Effects of iron-induced lipid peroxidation and of acidosis on choline uptake by synaptosomes

  • J. M. Cancela
  • J. Bralet
  • A. Beley
Original Articles


The effects of iron-induced lipid peroxidation and of lactic acidosis on [3H]choline uptake were investigated on crude synaptosomes prepared from rat cerebral cortices. Fe2+-induced lipid peroxidation as evidenced from the production of thiobarbituric acid reactives substances (TBARS) was correlated with a decrease in high-affinity choline uptake (HACU). Trolox C, a free radical scavenger, prevented both Fe2+-induced TBARS production and decrease in HACU. Lactic acidosis (pH 6.0 for 30 or 60 min) increased the TBARS production with concomitant decrease in HACU (−48%, −78%, respectively). The acidosis dependent decrease was not reversible following pH 7.4 readjustment after 60 min acidosis. It was not prevented by trolox C, although trolox C inhibited the acidosis-induced production of TBARS. The results suggest that the contribution of acidosis to peroxidative damages is probably of less importance in comparison to other cytotoxic mechanisms.

Key Words

Acidosis lipid peroxidation choline uptake synaptosomes 


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  1. 1.
    Siesjö, B. K. 1988. Acidosis and ischemic brain damage. Neurochem. Pathol. 9:31–88.PubMedGoogle Scholar
  2. 2.
    Marie, C., and Bralet, J. 1991. Blood glucose level and morphological brain damage following cerebral ischemia. Cerebrovasc. Brain Metab. Rev. 3:29–37.PubMedGoogle Scholar
  3. 3.
    Barber, A. A. 1963. Addendum: Mechanisms of lipid peroxide formation in rat tissue homogenates. Radiat. Res. Suppl. 3:33–43.PubMedGoogle Scholar
  4. 4.
    Bernheim, F. 1963. Biochemical implications of pro-oxidants and antioxidants. Radiat. Res. Suppl. 3:17–32.PubMedGoogle Scholar
  5. 5.
    Siesjö, B. K., Bendek, G., Koide, T., Westerberg, E., and Wicloch, T. 1985. Influence of acidosis on lipid peroxidation in brain tissues in vitro. J. Cereb. Blood Flow Metab. 5:253–258.PubMedGoogle Scholar
  6. 6.
    Rehncrona, S., Hauge, H. N., and Siesjö, B. K. 1989. Enhancement of iron-catalysed free radical formation by acidosis in brain homogenates: differences in effect by lactic acid and CO2. J. Cereb. Blood Flow Metab. 9:65–70.PubMedGoogle Scholar
  7. 7.
    Bralet, J., Bouvier, C., Schreiber, L., and Boquillon, M. 1991. Effect of acidosis on lipid peroxidation in brain slices. Brain Res. 539:175–177.PubMedGoogle Scholar
  8. 8.
    Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.PubMedGoogle Scholar
  9. 9.
    Buege, J. A., and Aust, S. D. 1978. Microsomal lipid peroxidation. Methods. Enzymol. 52:302–310.PubMedGoogle Scholar
  10. 10.
    Yagi, K. 1976. A simple fluorometric assay for lipoperoxide in blood plasma. Biochem. Med. 15:212–216.PubMedGoogle Scholar
  11. 11.
    Yamamura, H. I., and Snyder S. H. 1973. High affinity transport of choline into synaptosomes of rat brain. J. Neurochem. 21:1355–1374.PubMedGoogle Scholar
  12. 12.
    Minotti, G., and Aust, S. D. 1989. The role iron in oxygen radical mediated lipid peroxidation. Chem.-Biol.-Inter. 71:1–19.Google Scholar
  13. 13.
    Burton, G. W., and Ingold, K. U. 1989. Autoxidation of biological molecules. I: The antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro. J. Am. Chem. Soc. 103:6472–6477.Google Scholar
  14. 14.
    Dabrowiecki, Z., Gordon-Majszak, W., and Lazarewicz, J. 1985. Effects of lipid peroxidation on neurotransmitters uptake by rat synaptosomes. Pol. J. Pharmacol. Pharm. 37:325–331.PubMedGoogle Scholar
  15. 15.
    Braughler, J. M. 1985. Lipid peroxidation-induced inhibition of γ aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids. J. Neurochem. 44:1282–1288.PubMedGoogle Scholar
  16. 16.
    Debler, E. A., Sershen, H., Lajtha, A., and Genaro, J. F. 1986. Superoxide radical-mediated alteration of synaptosome membrane structure and high affinity γ [14C] aminobutyric acid uptake. J. Neurochem. 47:1804–1813.PubMedGoogle Scholar
  17. 17.
    Rafalowska, U., Liu, G. J., and Floyd, R. A. 1989. Peroxidation induced changes in synaptosomal transport of dopamine and γ aminobutyric acid. Free. Radical Biol. Med. 6:485–492.Google Scholar
  18. 18.
    Ramassamy, C., Naudin, B., Christen, Y., Clostre, F., and Costentin, J. 1992. Prevention by Ginkgo Biloba extract (EGb 761) and trolox C of the decrease in synaptosomal dopamine or serotonin uptake following incubation. Biochem. Pharmacol. 44:2395–2401.PubMedGoogle Scholar
  19. 19.
    Pastuszko, A., Gordon-Majszak, W., and Dabrowiecki, Z. 1983. Dopamine uptake in striatal synaptosomes exposed to peroxidation “in vitro”. Biochem. Pharmacol. 32:141–146.PubMedGoogle Scholar
  20. 20.
    Demopoulos, H., Flamm, E., Seligman, M., Power, R., Pietronigro, D., and Ransohoff, J. 1977. Molecular pathology of lipids in CNS membranes. Pages 491–508, In Jöbsis, F. F. (eds): oxygen and physiological function. Dallas, Texas, Professional Information Library.Google Scholar
  21. 21.
    Kogure, K., Arai, H., Abe, K., and Nakano, M. 1985. Free radical damage of the brain following ischemia. Prog. Brain. Res. 63:237–259.PubMedGoogle Scholar
  22. 22.
    Siesjö, B. K., Agardh, C.-D., and Bengtsson, F. 1989. Free radicals and brain damage. Cerebrovasc. Brain Metab. Rev. 1:165–211.Google Scholar
  23. 23.
    Roos, A. 1975. Intracellular pH and distribution of weak acids across cell membranes. A study of D- and L-lactate and of DMO in rat diaphragm. J. Physiol. 249:1–25.PubMedGoogle Scholar
  24. 24.
    Wills, E. D. 1965. Mechanisms of lipid peroxide formation in tissues. Role of metals and haematin proteins in the catalysis of the oxidation of unsaturated fatty acids. Biochim. Biophys. Acta. 98:238–251.PubMedGoogle Scholar
  25. 25.
    Pastuszko, A., Wilson, D. F., and Erecinska, M. 1982. Neurotransmitter metabolism in rat brain synaptosomes: effect of anoxia and pH. J. Neurochem. 38:1657–1667.PubMedGoogle Scholar
  26. 26.
    Braughler, J. M., and Hall, E. D. 1989. Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free. Radical Biol. Med., 6:289–301.Google Scholar
  27. 27.
    Kalimo, H., Rehncrona, S., Söderfeldt, B., Olsson, Y., and Siesjö, B. K. 1981. Brain lactic acidosis and ischemic cell damage: 2 Histopathology. J. Cereb. Blood Flow Metab. 1:313–327.PubMedGoogle Scholar
  28. 28.
    Hansen, A. J. 1985. Effects of anoxia on ion distribution in the brain. Physiol. Rev. 65:101–148.PubMedGoogle Scholar
  29. 29.
    Walz, W., and Harold, D. E. 1990. Brain lactic acidosis and synaptic function. Can. J. Physiol. Pharmacol. 68:164–169.PubMedGoogle Scholar
  30. 30.
    Jakubovicz, D. E., and Klip, A. 1989. Lactic acid-induced swelling in C6 glial cells via Na+/H+ exchange. Brain. Res. 485:215–224.PubMedGoogle Scholar
  31. 31.
    Newman, G. C., Hospod, F. E., and Schissel, S. L. 1991. Ischemic brain slice glucose utilisation: Effects of slice thickness, aidosis, and K+. J. Cereb. Blood Flow Metab. 11:398–406.PubMedGoogle Scholar
  32. 32.
    Hillered, L., Ernster, L., and Siesjö, B. K. 1984. Influence of in vitro lactic acidosis and hypercapnia on respiratory activity of isolated rat brain mitochondria. J. Cereb. Blood Flow Metab. 4:430–437.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • J. M. Cancela
    • 1
  • J. Bralet
    • 1
  • A. Beley
    • 1
  1. 1.Laboratoire de PharmacodynamieFaculté de PharmacieDijon CedexFrance

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