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The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration

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Abstract

Hyperhomocysteinemia is associated with various pathologies including cardiovascular disease, stroke, and cognitive dysfunctions. Systemic administration of homocysteine can trigger seizures in animals, and patients with homocystinuria suffer from epileptic seizures. Available data suggest that homocysteine can be harmful to human cells because of its metabolic conversion to homocysteine thiolactone, a reactive thioester. A number of reports have demonstrated a reduction of Na+/K+-ATPase activity in cerebral ischemia, epilepsy and neurodegeneration possibly associated with excitotoxic mechanisms. The aim of this study was to examine the in vivo effects of d,l-homocysteine and d,l-homocysteine thiolactone on Na+/K+- and Mg2+-ATPase activities in erythrocyte (RBC), brain cortex, hippocampus, and brain stem of adult male rats. Our results demonstrate a moderate inhibition of rat hippocampal Na+/K+-ATPase activity by d,l-homocysteine, which however expressed no effect on the activity of this enzyme in the cortex and brain stem. In contrast,d,l-homocysteine thiolactone strongly inhibited Na+/K+-ATPase activity in cortex, hippocampus and brain stem of rats. RBC Na+/K+-ATPase and Mg2+-ATPase activities were not affected by d,l-homocysteine, while d,l-homocysteine thiolactone inhibited only Na+/K+-ATPase activity. This study results show that homocysteine thiolactone significantly inhibits Na+/K+-ATPase activity in the cortex, hippocampus, and brain stem, which may contribute at least in part to the understanding of excitotoxic and convulsive properties of this substance.

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Acknowledgment

This work was supported by the Ministry for Science, Technology, and Environment Protection of Serbia (Grants #145029B and #145014B).

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Authors and Affiliations

  1. Laboratory of Neurophysiology, Institute of Medical Physiology, School of Medicine, University of Belgrade, Višegradska 26/II, 11 000, Belgrade, Serbia

    Aleksandra Rašić-Marković, Olivera Stanojlović, Dragan Hrnčić & Dragan Djuric

  2. Institute of Chemistry, School of Medicine, University of Belgrade, 11 000, Belgrade, Serbia

    Danijela Krstić

  3. “Vinča” Institute of Nuclear Sciences, 11 000, Belgrade, Serbia

    Mirjana Čolović

  4. Serbian Academy of Sciences and Arts, 11 000, Belgrade, Serbia

    Veselinka Šušić

  5. Institute of Pathophysiology, School of Medicine, University of Belgrade, 11 000, Belgrade, Serbia

    Tatjana Radosavljević

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  1. Aleksandra Rašić-Marković
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Correspondence to Olivera Stanojlović.

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Rašić-Marković, A., Stanojlović, O., Hrnčić, D. et al. The activity of erythrocyte and brain Na+/K+ and Mg2+-ATPases in rats subjected to acute homocysteine and homocysteine thiolactone administration. Mol Cell Biochem 327, 39–45 (2009). https://doi.org/10.1007/s11010-009-0040-6

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