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Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz


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Volume 4, Issue 3

Issues

Volume 10 (2015)

Brain monoamine oxidase A in hyperammonemia is regulated by NMDA receptors

Elena Kosenko
  • Laboratory of Metabolic Modelling and Bioinformatics, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia
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/ Yury Kaminsky
  • Laboratory of Metabolic Modelling and Bioinformatics, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia
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Published Online: 2009-07-26 | DOI: https://doi.org/10.2478/s11535-009-0016-2

Abstract

Mitochondrial enzyme monoamine oxidase A (MAO-A) generates hydrogen peroxide (H2O2) and is up-regulated by Ca2+ and presumably by ammonia. We hypothesized that MAO-A may be under the control of NMDA receptors in hyperammonemia. In this work, the in vivo effects of single dosing with ammonia and NMDA receptor antagonist MK-801 and the in vitro effect of Ca2+ on MAO-A activity in isolated rat brain mitochondria were studied employing enzymatic procedure. Intraperitoneal injection of rats with ammonia led to an increase in MAO-A activity in mitochondria indicating excessive H2O2 generation. Calcium added to isolated mitochondria stimulated MAO-A activity by as much as 84%. MK-801 prevented the in vivo effect of ammonia, implying that MAO-A activation in hyperammonemia is mediated by NMDA receptors. These data support the conclusion that brain mitochondrial MAO-A is regulated by the function of NMDA receptors. The enzyme can contribute to the oxidative stress associated with hyperammonemic conditions such as encephalopathy and Alzheimer’s disease. The attenuation of the oxidative stress highlights MAO-A inactivation and NMDA receptor antagonists as sources of novel avenues in the treatment of mental disorders.

Keywords: Ammonia; Hyperammonemia; Monoamine oxidase; NMDA receptor; Brain mitochondria; Hydrogen peroxide

  • [1] Westlund K.N., Krakower T.J., Kwan S.W., Abell C.W., Intracellular distribution of monoamine oxidase A in selected regions of rat and monkey brain and spinal cord, Brain Res., 1993, 612, 221–230 http://dx.doi.org/10.1016/0006-8993(93)91664-ECrossrefGoogle Scholar

  • [2] Levitt P., Pintar J.E., Breakefield X.O., Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons, Proc. Natl. Acad. Sci. USA, 1982, 79, 6385–6389 http://dx.doi.org/10.1073/pnas.79.20.6385CrossrefGoogle Scholar

  • [3] Mousseau D.D., Baker G.B., Butterworth R.F., Increased density of catalytic sites and expression of brain monoamine oxidase A in humans with hepatic encephalopathy, J. Neurochem., 1997, 68, 1200–1208 Google Scholar

  • [4] Rao V.L., Nitric oxide in hepatic encephalopathy and hyperammonemia, Neurochem. Int., 2002, 41, 161–170 http://dx.doi.org/10.1016/S0197-0186(02)00038-4CrossrefGoogle Scholar

  • [5] Hermenegildo C., Monfort P., Felipo V., Activation of NMDA receptors in rat brain in vivo following acute ammonia intoxication. Characterization by in vivo brain microdialysis, Hepatology, 2000, 31, 709–715 http://dx.doi.org/10.1002/hep.510310322CrossrefGoogle Scholar

  • [6] Kosenko E., Kaminsky Y., Grau E., Minana M.D., Marcaida G., Grisolia S., et al., Brain ATP depletion induced by acute ammonia intoxication in rats is mediated by activation of the NMDA receptor and Na+,K+-ATPase, J. Neurochem., 1994, 63, 2172–2178 http://dx.doi.org/10.1046/j.1471-4159.1994.63062172.xCrossrefGoogle Scholar

  • [7] Malenka R.C., The role of postsynaptic calcium in the induction of long-term potentiation, Mol. Neurobiol., 1991, 5, 289–295 http://dx.doi.org/10.1007/BF02935552CrossrefGoogle Scholar

  • [8] Choi D.W., Glutamate neurotoxicity and diseases of the nervous system, Neuron, 1988, 1, 623–634 http://dx.doi.org/10.1016/0896-6273(88)90162-6CrossrefGoogle Scholar

  • [9] Meldrum B.S., The role of glutamate in epilepsy and other CNS disorders, Neurology, 1994, 44, 14–23 Google Scholar

  • [10] Minana M.D., Llansola M., Hermenegildo C., Cucarella C., Montoliu C., Kosenko E., et al., Glutamate and muscarinic receptors in the molecular mechanisms of acute ammonia toxicity and of its prevention, Adv. Exp. Med. Biol., 1997, 420, 45–56 Google Scholar

  • [11] Ward M.W., Kushnareva Y., Greenwood S., Connolly C.N., Cellular and subcellular calcium accumulation during glutamate-induced injury in cerebellar granule neurons, J. Neurochem., 2005, 92, 1081–1090 http://dx.doi.org/10.1111/j.1471-4159.2004.02928.xCrossrefGoogle Scholar

  • [12] Kosenko E., Kaminsky Y., Stavroskaya I.G., Felipo V., Alteration of mitochondrial calcium homeostasis by ammonia-induced activation of NMDA receptors in rat brain in vivo, Brain. Res., 2000, 880, 139–146 http://dx.doi.org/10.1016/S0006-8993(00)02785-2CrossrefGoogle Scholar

  • [13] Kosenko E., Kaminsky Y., Kaminsky A., Valencia M., Lee L., Hermenegildo C., et al., Superoxide production and antioxidant enzymes in ammonia intoxication in rats, Free Radic. Res., 1997, 27, 637–644 http://dx.doi.org/10.3109/10715769709097867CrossrefGoogle Scholar

  • [14] Kosenko E., Kaminski Y., Lopata O., Muravyov N., Felipo V., Blocking NMDA receptors prevents the oxidative stress induced by acute ammonia intoxication, Free Radic. Biol. Med., 1999, 26, 1369–1374 http://dx.doi.org/10.1016/S0891-5849(98)00339-6CrossrefGoogle Scholar

  • [15] Kosenko E., Venediktova N., Kaminsky Y., Montoliu C., Felipo V., Sources of oxygen radicals in brain in acute ammonia intoxication in vivo, Brain Res., 2003, 981, 193–200 http://dx.doi.org/10.1016/S0006-8993(03)03035-XCrossrefGoogle Scholar

  • [16] Kosenko E., Venediktova N., Kaminsky Y., Montoliu C., Felipo V., Preparation and handling of brain mitochondria useful to study uptake and release of calcium, Brain Res. Brain Res. Protoc., 2001, 7, 248–254 http://dx.doi.org/10.1016/S1385-299X(01)00071-XCrossrefGoogle Scholar

  • [17] Lowry O.H., Rosenbrough N.J., Farr A.L., Randall R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem., 1951, 193, 265–275 Google Scholar

  • [18] Kosenko E.A., Venediktova N.I., Kaminsky Yu. G., Calcium and ammonia stimulate monoamine oxidase A activity in brain mitochondria, Izv. Akad. Nauk. Ser. Biol., 2003, 30, 542–546 (in Russian) Google Scholar

  • [19] Cao X., Wei Z., Gabriel G.G., Li X., Mousseau D.D., Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease-related pathology, BMC Neuroscience, 2007, 8, 73 http://dx.doi.org/10.1186/1471-2202-8-73CrossrefGoogle Scholar

  • [20] Adam-Vizi V., Production of reactive oxygen species in brain mitochondria: contribution by electron transport chain and non-electron transport chain sources, Antioxid. Redox Signal., 2005, 7, 1140–1149 http://dx.doi.org/10.1089/ars.2005.7.1140CrossrefGoogle Scholar

  • [21] Rokicki W., Rokocki M., Kaminski K., Peciak B., Gebska E., Experimental studies of the pathomechanism of portal encephalopathy. I. Changes in monoamine oxidase (MAO) activity in the cerebral cortex and cerebellum of rats after portacaval shunt, Neuropathol. Pol., 1989, 27, 199–207 Google Scholar

  • [22] Rao V.L.R., Qureshi I.A., Butterworth R.F., Activities of monoamine oxidase-A and -B are altered in the brains of congenitally hyperammonemic sparse-fur (spf) mice, Neurosci. Lett., 1994, 170, 27–30 http://dx.doi.org/10.1016/0304-3940(94)90230-5CrossrefGoogle Scholar

  • [23] Sadadivudu B., Murthy R.K.C., Effects of ammonia on monoamine oxidase and enzymes of GABA metabolism in mouse brain, Arch. Int. Physiol. Biochim., 1978, 86, 67–82 http://dx.doi.org/10.3109/13813457809069884CrossrefGoogle Scholar

  • [24] Egashira T., Sakai K., Sakurai M., Takayama F., Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain, Biol. Trace Elem. Res., 2003, 94, 203–211 http://dx.doi.org/10.1385/BTER:94:3:203CrossrefGoogle Scholar

About the article

Published Online: 2009-07-26

Published in Print: 2009-09-01


Citation Information: Open Life Sciences, Volume 4, Issue 3, Pages 321–326, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-009-0016-2.

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© 2009 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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