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Iron and Neurotransmitter Function in the Brain

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Metals and Oxidative Damage in Neurological Disorders

Abstract

Iron involvement in basic cell functions as well as in many human diseases has been described in excellent reviews (see, for example, Lauffer, 1992). Neural cells, like any other cell type, require iron for DNA synthesis, mitochondrial respiration, and other vitally important reactions. They are, on the other hand, susceptible to iron toxicity caused by iron overload. But the most remarkable characteristic of neural cells is observed only on the metacellular level: Neurons are organized in a network, which is used for collecting and analyzing of incoming information and producing an adequate response. This response can include regulation of non-neuronal systems.

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References

  • Adam-Visi, V, 1992, External Ca2+-independent release of neurotransmitters. J. Neurochem. 58:395–405.

    Article  Google Scholar 

  • Adams, J. A., and Taylor, S. S., 1993, Divalent metal ions influence catalysis and active-site accessibility in the cAMP-dependent protein kinase, Protein Sci. 2:2177–2186.

    Article  PubMed  CAS  Google Scholar 

  • Alcain, F. J., Low, H., and Crane, F. L., 1994, Iron at the cell surface controls DNA synthesis in CCI 39 cells, Biochem. Biophys. Res. Commun. 203:16–21.

    Article  PubMed  CAS  Google Scholar 

  • Alcantara, O., Obeid, L., Hannun, Y, Ponka, P., and Boldt, D. H., 1994, Regulation of protein kinase C (PKC) expression by iron: Effect on different iron compounds on PKC-ß and PKC-alpha gene expression and role of the 5′-flanking region of the PKC-ß gene in the response to ferric transferrin, Blood 84:3510–3517.

    PubMed  CAS  Google Scholar 

  • Allen, D. R., Wallis, G. L., and McCay, P. B., 1994, Catechol adrenergic agents enhance hydroxyl radical generation in xanthine oxidase systems containing ferritin: Implications for ischemia/reperfusion, Arch. Biochem. Biophys. 315:235–243.

    Article  PubMed  CAS  Google Scholar 

  • Almas, B., Le Bourdelles, B., Flatmark, T., Mallet, J., and Haavik, J., 1992, Regulation of recombinant human tyrosine hydroxylase isozymes by catecholamine binding and phosphorylation. Structure/ activity studies and mechanistic implications, Eur. J. Biochem. 209:249–255.

    Article  PubMed  CAS  Google Scholar 

  • Anghileri, L. J., Maincent, P., and Cordova-Martinez, A., 1993, On the mechanism of soft tissue calcification induced by complexed iron, Exp. Toxicol. Pathol. 45:365–368.

    Article  PubMed  CAS  Google Scholar 

  • Bading, H., Ginty, D. D., and Greenberg, M. E., 1993, Regulation of gene expression in hippocampal neurons by distinct calcium signaling pathways, Science 260:181–186.

    Article  PubMed  CAS  Google Scholar 

  • Beard, J., 1987, Feed efficiency and norepinephrine turnover in iron deficiency, Proc. Soc. Exp. Biol. Med. 184:337–344.

    PubMed  CAS  Google Scholar 

  • Beard, J., Tobin, B., and Smith, S. M., 1988, Norepinephrine turnover in iron deficiency at three environmental temperatures, Am. J. Physiol. 255:R90–6.

    Google Scholar 

  • Beard, J. L., Tobin, B. W., and Smith, S. M., 1990, Effects of iron repletion and correction of anemia on norepinephrine turnover and thyroid metabolism in iron deficiency, Proc. Soc. Exp. Biol. Med. 193:306–312.

    PubMed  CAS  Google Scholar 

  • Beard, J. L., Connor, J. D., and Jones, B. C, 1993, Brain iron: location and function, Prog. Food Nutr. Sci. 17:183–221.

    PubMed  CAS  Google Scholar 

  • Beard, J. L., Chen, Q., Connor, J., and Jones, B. C, 1994, Altered monamine metabolism in caudate-putamen of iron-deficient rats, Pharmacol. Biochem. Behav. 48:621–624.

    Article  PubMed  CAS  Google Scholar 

  • Ben-Shachar, D., Tovi, A., and Youdim, M. B. H., 1993, Iron regulation of dopaminergic transmission: relevance to movement disorders, in: Iron in Central Nervous System Disorders (P. Riederer and M. B. H. Youdim, eds.), Springer-Verlag, Wien, pp. 55–66.

    Chapter  Google Scholar 

  • Ben-Shachar, D., Zuk, R., and Glinka, Y, 1994, Dopamine neurotoxicity: inhibition of mitochondrial respiration, J. Neurochem. 64:718–723.

    Article  Google Scholar 

  • Braughler, J. M., Duncan, L. A., and Chase, R. L., 1985, Interaction of lipid peroxidation and calcium in the pathogenesis of neuronal injury, Cent. Nerv. Syst. Trauma 2:269–283.

    PubMed  CAS  Google Scholar 

  • Buccigross, J. M., and Nelson, D. J., 1986, EPR studies show that all lanthanides do not have the same order of binding to calmodulin, Biochem. Biophys. Res. Commun. 138:1243–1249.

    Article  PubMed  CAS  Google Scholar 

  • Buccigross, J. M., and Nelson, D. J., 1988, Interactions of spin-labeled calmodulin with trifluoperazine and phosphodiesterase in the presence of Ca(II), Cd(II), La(III), Tb(III), and Lu(III), J. Inorg. Biochem. 33:139–147.

    Article  PubMed  CAS  Google Scholar 

  • Caporaso, G. L., Takei, K., Gandy, S. E., Matteoli, M., Mundigl, O., Greengard, P., and De Camilli, P., 1994, Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer ß/A4 amyloid precursor protein, J. Neurosci, 14:3122–3138.

    PubMed  CAS  Google Scholar 

  • Carraway, R. E., Mitra, S. P., and Honeyman, T. W, 1993, Effects of GTP analogs and metal ions on the binding of neurotensin to porcine brain membranes, Peptides 14:37–45.

    Article  PubMed  CAS  Google Scholar 

  • Carter, D. A., 1992, Neurotransmitter-stimulated immediate-early gene responses are organized through differential post-synaptic receptor mechanisms, Brain Res. Mol. Brain Res. 16:111–118.

    Article  PubMed  CAS  Google Scholar 

  • Chao, M. V, 1994, Mechanism of action of neurotrophin receptors, Neuropsychopharmacology 10:109S.

    Google Scholar 

  • Cohen, G., and Werner, P., 1994, Free radicals, oxidative stress, and neurodegeneration, in: Neurodegenerative Diseases (D. B. Calne, ed.), W. B. Saunders, Philadelphia, pp. 139–162.

    Google Scholar 

  • Cotterill, L. A., Gower, J. D., Clark, P. K., Fuller, B. J., Thorniley, M. S., Goddard, J. G., and Green, C. J., 1993, Reoxygenation following hypoxia stimulates lipid peroxidation and phosphatidylinositol breakdown, Biochem. Pharmacol. 45:1947–1951.

    Article  PubMed  CAS  Google Scholar 

  • Crichton, R. R., and Ward, R. J., 1992, Structure and molecular biology of iron binding proteins and the regulation of “free” iron pools, in: Iron and Human Disease (R. B. Lauffer, ed.), CRC Press, Boca Raton, Florida, pp. 23–75.

    Google Scholar 

  • Daniel, H., Hemart, N., Jaillard, D., and Crepel, E, 1993, Long-term depression requires nitric oxide and guanosine 3′:5′ cyclic monophosphate production in rat cerebellar Purkinje cells, Eur. J. Neurosci. 5:1079–1082.

    Article  PubMed  CAS  Google Scholar 

  • Davis, G. W., and Murphey, R. K., 1994, Long-term regulation of short-term transmitter release properties: retrograde signaling and synaptic development, Trends Neurosci. 17:9–13.

    Article  PubMed  CAS  Google Scholar 

  • Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S., and Snyder, S. H., 1991, Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures, Proc. Natl. Acad. Sci. USA 88:6368–6371.

    Article  PubMed  CAS  Google Scholar 

  • De Sousa, E. B., and Cunnigham, E. T., Jr., 1994, Mapping of interleukin-1 receptors in the central nervous system: autoradiographic localization and in situ hybridization studies, Neuropsychopharmacology 10:136S.

    Google Scholar 

  • Eisenstein, R. S., Tuazon, R T., Schalinske, K. L., Anderson, S. A., and Traugh, J. A., 1993, Iron-responsive element-binding protein. Phosphorylation by protein kinase C., J. Biol. Chem. 268:27363–27370.

    PubMed  CAS  Google Scholar 

  • Emould, A. P., Ferry, G., Barret, J. M., Genton, A., and Boutin, J. A., 1993, Purification and characterization of the major tyrosine protein kinase from the human promyelocytic cell line, HL60, Eur. J. Biochem. 214:503–514.

    Article  Google Scholar 

  • Evans, T. C., and Mackler, B., 1985, Effect of iron deficiency on energy conservation in rat liver and skeletal muscle submitochondrial particles, Biochem. Med. 34:93–99.

    Article  PubMed  CAS  Google Scholar 

  • Ferrendelli, J. A., Chang, M. M., and Kinscherf, D. A., 1974, Elevation of cyclic GMP levels in central nervous system by excitatory and inhibitory amino acids, J. Neurochem. 22:535–540.

    Article  PubMed  CAS  Google Scholar 

  • Garriga, G., Desai, C., and Horvitz, H. R., 1993, Cell interactions control the direction of outgrowth, branching and fasciculation of the HSN axons of Caenorhabditis elegans, Development 117:1071–1087.

    PubMed  CAS  Google Scholar 

  • Gibbon, B. C., and Kropt, D. L., 1994, Cytosolic pH gradients associated with tip growth, Science 263:1419–1421.

    Article  PubMed  CAS  Google Scholar 

  • Girotti, A. W., Thomas, J. P., and Jordan, J. E., 1986, Xanthine oxidase-catalyzed crosslinking of cell membrane proteins, Arch. Biochem. Biophys. 251:639–653.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein, G. W., 1993, Evidence that lead acts as a calcium substitute in second messenger metabolism, Neurotoxicology 14:97–101.

    PubMed  CAS  Google Scholar 

  • Gomez, T. M., and Letourneau, P. C., 1994, Filopodia initiate choices made by sensory neuron growth cones at laminin/fibronectin borders in vitro, J. Neurosci. 14:5959–5972.

    PubMed  CAS  Google Scholar 

  • Griscavage, J. M., Fukuto, J. M., Komori, Y, and Ignarro, L. J., 1994, Nitric oxide inhibits neuronal nitric oxide synthase by interacting with the heme prosthetic group. Role of tetrahydrobiopterin in modulating the inhibitory action of nitric oxide, J. Biol. Chem. 269:21644–21649.

    PubMed  CAS  Google Scholar 

  • Gyenes, M., Wang, Q., Gibbs, T. T., and Farb, D. H., 1994, Phosphorylation factors control neurotransmitter and neuromodulator actions at the gamma-aminobutyric acid type A receptor, Mol. Pharmacol. 46:542–549.

    PubMed  CAS  Google Scholar 

  • Hamelin, M., Zhou, Y, Su, I. M., Scott, I. M., and Culotti, J. G., 1993, Expression of the UNC-5 guidance receptor in the touch neurons of C. elegans steers their axons dorsally, Nature 364:327–330.

    Article  PubMed  CAS  Google Scholar 

  • Hara, H., Kato, H., Araki, T., Onodera, H., and Kogure, K., 1991, Involvement of lipid peroxidation and inhibitory mechanisms on ischemic neuronal damage in gerbil hippocampus: Quantitative autoradiographic studies on second messenger and neurotransmitter systems, Neuroscience 42:159–169.

    Article  PubMed  CAS  Google Scholar 

  • Haug, A., Shi, B., and Vitorello, V, 1994, Aluminum interaction with phosphoinositide-associated signal transduction, Arch. Toxicol. 68:1–7.

    Article  PubMed  CAS  Google Scholar 

  • Hayes, G., Biden, T. J., Selbie, L. A., and Shine, J., 1992, Structural subtypes of the dopamine D2 receptor are functionally distinct: expression of the cloned D2A and D2B subtypes in a heterologous cell line, Mol. Endocrinol. 6:920–926.

    Article  PubMed  CAS  Google Scholar 

  • Hedberg, K. K., Birrell, G. B., and Griffith, O. H., 1991, Phorbol ester-induced actin cytoskeletal reorganization requires a heavy metal ion, Cell Regul. 2:1067–1079.

    PubMed  CAS  Google Scholar 

  • Hedberg, K. K., Birrell, G. B., Mobley, P. L., and Griffith, O. H., 1994, Transition metal chelator TPEN counteracts phorbol ester-induced actin cytoskeletal disruption in C6 rat glioma cells without inhibiting activation or translocation of protein kinase C., J. Cell Physiol. 158:337–346.

    Article  PubMed  CAS  Google Scholar 

  • Higashijima, T, Ferguson, K. M., Sternweis, P. C., Smigel, M. D., and Gilman, A. G., 1987, Effects of Mg2+ and the beta gamma-subunit complex on the interactions of guanine nucleotides with G proteins, J. Biol. Chem. 262:762–766.

    PubMed  CAS  Google Scholar 

  • Hill, J. M., 1985, Iron concentration reduced in ventral pallidum, globus pallidus, and substantia nigra by GABA-transaminase inhibitor, gamma-vinyl GAB A, Brain Res. 342:18–25.

    Article  PubMed  CAS  Google Scholar 

  • Hurtley, S. M., 1993, Membrane proteins involved in targeted membrane fusion, Trends Biol. Sci. 18:453–455.

    Article  CAS  Google Scholar 

  • Ihle, J. N., Witthuhm, B. R., Ouelle, F. W., Yamamoto, K., Thierfelder, W. E., Kreider, B., and Silvennoinen, O., 1992, Signalling by the cytokine receptor superfamily: JAKs and STATs, Trends Biol. Sci. 19:222–227.

    Article  Google Scholar 

  • Kardos, J., Elster, L., Damgaard, L, Krogsgaard-Larsen, P., and Schousboe, A., 1994, Role of GABAB receptors in intracellular Ca2+ homeostasis and possible interaction between GABAA and GABAB receptors in regulation of transmitter release in cerebellar granule neurons, J. Neurosci. Res. 39:646–655.

    Article  PubMed  CAS  Google Scholar 

  • Karschin, A., Wischmeyer, E., Davidson, N., and Lester, H. A., 1994, Fast inhibition of inwardly rectifying K+ channels by multiple neurotransmitter receptors in Oligodendroglia, Eur. J. Neurosci. 6:1756–1764.

    Article  PubMed  CAS  Google Scholar 

  • Kebabian, J. W., 1994, Neurotransmitter receptors in neurodegeneration, in: Neurodegenerative Diseases (D. B. Calne, ed.), W. B. Saunders, Philadelphia, pp. 119–128.

    Google Scholar 

  • King, M. M., and Huang, C. Y., 1984, The calmodulin-dependent activation and deactivation of the phosphoprotein phosphatase, calcineurin, and the effect of nucleotides, pyrophosphate, and divalent metal ions. Identification of calcineurin as a Zn and Fe metalloenzyme, J. Biol Chem. 259:8847–8856.

    PubMed  CAS  Google Scholar 

  • Korge, P., and Campbell, K. B., 1993, The effect of changes in iron redox state on the activity of enzymes sensitive to modification of SH groups, Arch. Biochem. Biophys. 304:420–428.

    Article  PubMed  CAS  Google Scholar 

  • Kuhn, D. M., Ruskin, B., and Lovenberg, W., 1980, Tryptophan hydroxylase. The role of oxygen, iron, and sulfhydryl groups as determinants of stability and catalytic activity, J. Biol. Chem. 255:4137–4143.

    PubMed  CAS  Google Scholar 

  • Landgraf, W., Regulla, S., Meyer, H. E., and Hofmann, F., 1991, Oxidation of cysteines activates cGMP-dependent protein kinase, J. Biol. Chem. 266:16305–16311.

    PubMed  CAS  Google Scholar 

  • Laufer, R., and Changeux, J. P., 1989, Activity-dependent regulation of gene expression in muscle and neuronal cells, Mol. Neurobiol. 3:1–53.

    Article  PubMed  CAS  Google Scholar 

  • Lauffer, R. B., 1992, Iron, aging, and human disease: historical background and new hypotheses, in: Iron and Human Disease (R. B. Lauffer, ed.), CRC Press, Boca Raton, FL, pp. 1–20.

    Google Scholar 

  • Leclerc, L., Marden, M., and Poyart, C., 1991, Inhibition of the erythrocyte (Ca2+ + Mg2+)-ATPase by nonheme iron, Biochim. Biophys. Acta. 1062:35–38.

    Article  PubMed  CAS  Google Scholar 

  • Lei, S. Z., Pan, Z. H., Aggarwal, S. K., Chen, H. S., Hartman, J., Sucher, N. J., and Lipton, S. A., 1992, Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex, Neuron 8:1087–1099.

    Article  PubMed  CAS  Google Scholar 

  • Li, C. Y., Watkins, J. A., Hamazaki, S., Altazan, J. D., and Glass, J., 1995, Iron binding, a new function for the reticulocyte endosome H+-ATPase, Biochemistry 34:5130–5136.

    Article  PubMed  CAS  Google Scholar 

  • Lin, C. H., and Forscher, P., 1993, Cytoskeleton remodeling during growth cone-target interactions, J. Cell Biol. 121:1369–1383.

    Article  PubMed  CAS  Google Scholar 

  • Lindsay, R. M., Wiegand, S. J., Altar, C. A., and DiStephano, P. S., 1994, Neurotrophic factors: from molecule to man, Trends Neurosci. 17:182–190.

    Article  PubMed  CAS  Google Scholar 

  • Lippe, G., Comelli, M., Mazzilis, D., Sala, F. D., and Mavelli, I., 1991, The inactivation of mitochondrial Fl ATPase by H202 is mediated by iron ions not tightly bound in the protein, Biochem. Biophys. Res. Commun. 181:764–770.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., and Moser, A., 1994, Actions of redox-related congeners of nitric oxide at the NMDA receptor, Neuropharmacology 33:1229–1233.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., Choi, Y. B., Pan, Z. H., Lei, S. Z., Chen, H. S., Sucher, N. J., Loscalzo, J., Singel, D. J., and Moser, A., 1993, A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds, Nature 364:626–632.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., Singel, D. J., and Moser, A., 1994a, Nitric oxide in the central nervous system, Prog. Brain Res. 103:359–364.

    Article  PubMed  CAS  Google Scholar 

  • Lipton, S. A., Yeh, M., and Dreyer, E. B., 1994b, Update on current models of HIV-related neuronal injury: Platelet-activating factor, arachidonic acid and nitric oxide, Adv. Neuroimmunol. 4:181–188.

    Article  PubMed  CAS  Google Scholar 

  • Liu, F. C., Takahashi, H., McKay, R. D., and Graybiel, A. M., 1995, Dopaminergic regulation of transcription factor expression in organotypic cultures of developing striatum, J. Neurosci. 15:2367–2384.

    PubMed  CAS  Google Scholar 

  • Liu, J., and Mori, A., 1993, Monoamine metabolism provides an antioxidant defense in the brain against oxidant- and free radical-induced damage, Arch. Biochem. Biophys. 302:118–127.

    Article  PubMed  CAS  Google Scholar 

  • Ludlam, W. H., and Kessler, J. A., 1993, Leukemia inhibitory factor and ciliary neurotrophic factor regulate expression of muscarinic receptors in cultured sympathetic neurons, Dev. Biol. 155:497–506.

    Article  PubMed  CAS  Google Scholar 

  • Manne, V., and Kung, H. F, 1985, Effect of divalent metal ions and glycerol on the GTPase activity of H-ras proteins, Biochem. Biophys. Res. Commun. 128:1440–1446.

    Article  PubMed  CAS  Google Scholar 

  • Marti, H. H., Jung, H. H., Pfeilschifter, J., and Bauer, C., 1994, Hypoxia and cobalt stimulate lactate dehydrogenase (LDH) activity in vascular smooth muscle cells, Pflugers Arch. 429:216–222.

    Article  PubMed  CAS  Google Scholar 

  • Masliah, E., Hansen, L., Mallory, M., Albright, T., and Terry, R. D., 1991, Abnormal brain spectrin immunoreactivity in sprouting neurons in Alzheimer disease, Neurosci. Lett. 129:1–5.

    Article  PubMed  CAS  Google Scholar 

  • Mattammal, M. B., Strong, R., Lakshmi, V. M., Chung, H. D., and Stephenson, A. H., 1995, Prostaglandin H synthetase-mediated metabolism of dopamine: Implication for Parkinson’s disease, J. Neurochem. 64:1645–1654.

    Article  PubMed  CAS  Google Scholar 

  • Maurer, M. C., Grisham, C. M., and Sando, J. J., 1992, Activation and inhibition of protein kinase C isozymes alpha and beta by Gd3+, Arch. Biochem. Biophys. 298:561–568.

    Article  PubMed  CAS  Google Scholar 

  • Meij, J. T., Suzuki, S., Panagia, V, and Dhalla, N. S., 1994, Oxidative stress modifies the activity of cardiac sarcolemmal phospholipase C., Biochim. Biophys. Acta. 1199:6–12.

    Article  PubMed  CAS  Google Scholar 

  • Memo, M., Bovolin, P., Costa, E., and Grayson, D. R., 1991, Regulation of gamma-aminobutyric acid A receptor subunit expression by activation of N-methyl-D-aspartate-selective glutamate receptors, Mol. Pharmacol. 39:599–603.

    PubMed  CAS  Google Scholar 

  • Monasterio, O., and Timasheff, S. N., 1985, Role of the dianionic form of the GTP gamma-phosphate in the polymerization process of tubulin, Arch. Biol. Med. Exp. (Santiago) 18:325–329.

    CAS  Google Scholar 

  • Montastruc, J. L., Galitzky, J., Berlan, M., and Montastruc, P., 1993, Mechanism of receptor regulation during repeated administration of drugs, Therapie 48:421–426.

    PubMed  CAS  Google Scholar 

  • Montpied, P., Ginns, E. I., Martin, B. M., Roca, D., Farb, D. H., and Paul, S. M., 1991, gamma-Aminobutyric acid (GAB A) induces a receptor-mediated reduction in GABAA receptor alpha subunit messenger RNAs in embryonic chick neurons in culture, J. Biol. Chem. 266:6011–6014.

    PubMed  CAS  Google Scholar 

  • Moser, A., and Schuster, O., 1990, Iron inhibits D-1 dopamine receptor coupled adenylate cyclase via G-proteins in the caudate nucleus of the rat, Biochem. Biophys. Res. Commun. 171:1372–1377.

    Article  PubMed  CAS  Google Scholar 

  • Nanji, A. A., Zhao, S., Lamb, R. G., Sadrzadeh, S. M., Dannenberg, A. J., and Waxman, D. J., 1993, Changes in microsomal phospholipases and arachidonic acid in experimental alcoholic liver injury: Relationship to cytochrome P-450 2E1 induction and conjugated diene formation, Alcohol Clin. Exp. Res. 17:589–603.

    Article  Google Scholar 

  • Nimura, E., Miura, K., Shinobu, L. A., and Imura, N., 1987, Enhancement of Ca2+-sensitive myosin ATPase activity by cadmium, Ecotoxicol. Environ. Safety 14:184–189.

    Article  PubMed  CAS  Google Scholar 

  • Orchinik, M., Weiland, N. G., and McEwen, B. S., 1994, Adrenalectomy selectively regulates GABA A receptor subunit expression in the hippocampus, Mol. Cell Neurosci. 5:451–458.

    Article  PubMed  CAS  Google Scholar 

  • Otto, D., and Unsicker, K., 1993, FGF-2-Mediated protection of cultured mesencephalic dopaminergic neurons against MPTP and MPP+: Specificity and impact of culture conditions, non-dopaminergic neurons, and astroglial cells, J. Neurosci. Res. 34:382–383.

    Article  PubMed  CAS  Google Scholar 

  • Pantopoulos, K., and Hentze, M. W., 1995, Nitric oxide signaling to iron regulatory protein: Direct control of ferritin mRNA translation and transferrin receptor mRNA stability in transfected fibroblasts, Proc. Natl. Acad. Sci. USA 92:1267–1271.

    Article  PubMed  CAS  Google Scholar 

  • Pathak, D. N., Roy, D., and Singh, R., 1984, Changes in the activity of gamma-amino butyric acid transaminase and succinic semialdehyde dehydrogenase in the cobalt and iron experimental epileptogenic foci in the rat brain, Biochem. Int. 9:59–68.

    PubMed  CAS  Google Scholar 

  • Payne, M. J., Woods, L. F., Gibbs, P., and Cammack, R., 1990, Electron paramagnetic resonance spectroscopic investigation of the inhibition of the phosphoroclastic system of Clostridium sporogenes by nitrite, J. Gen. Microbiol. 136:2067–2076.

    Article  PubMed  CAS  Google Scholar 

  • Pedigo, N. W, 1994, Neurotransmitter receptor plasticity in aging, Life Sci. 55:1985–1991.

    Article  PubMed  CAS  Google Scholar 

  • Pellmar, T. C., 1987, Peroxide alters neuronal excitability in the CA1 region of guinea-pig hippocampus in vitro, Neuroscience 23:447–456.

    Article  PubMed  CAS  Google Scholar 

  • Piani, D., Constam, D. B., Frei, K., and Fontana, A., 1994, Macrophages in brain: friends or enemies? News in Physiological Sciences 9:80–84.

    Google Scholar 

  • Price, D. J., and Joshi, J. G., 1984, Ferritin: protection of enzymatic activity against the inhibition by divalent metal ions in vitro, Toxicology 31:151–163.

    Article  PubMed  CAS  Google Scholar 

  • Qin, Z. H., Zhang, S. P., and Weiss, B., 1994, Dopaminergic and glutamatergic blocking drugs differentially regulate glutamic acid decarboxylase mRNA in mouse brain, Brain Res. Mol. Brain Res. 21:293–302.

    Article  PubMed  CAS  Google Scholar 

  • Rafalowska, U., Liu, G. J., and Floyd, R. A., 1989, Peroxidation induced changes in synaptosomal transport of dopamine and gamma-aminobutyric acid, Free Radic. Biol. Med. 6:485–492.

    Article  PubMed  CAS  Google Scholar 

  • Ramassamy, C., Girbe, F., Pincemail, J., Christen, Y, and Costentin, J., 1994, Modifications of the synaptosomal dopamine uptake and release by two systems generating free radicals: Ascorbic acid/Fe2+ and L-arginine/NADPH, Ann. N Y. Acad. Sci. 738:141–152.

    Article  PubMed  CAS  Google Scholar 

  • Rausch, W. D., Hirata, Y, Nagatsu, T., Riederer, R, and Jellinger, K., 1988, Tyrosine hydroxylase activity in caudate nucleus from Parkinson’s disease: Effects of iron and phosphorylating agents, J. Neurochem. 50:202–208.

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro, P., Wang, Y., Citron, B. A., and Kaufman, S., 1992, Regulation of recombinant rat tyrosine hydroxylase by dopamine, Proc. Natl. Acad. Sci. USA 89:9593–9597.

    Article  PubMed  CAS  Google Scholar 

  • Richard, S., Brion, J. P., Couck, A. M., and Flament-Durand, J., 1989, Accumulation of smooth endoplasmic reticulum in Alzheimer’s disease: New morphological evidence of axoplasmic flow disturbances, J. Submicrosc. Cytol. Pathol 21:461–467.

    PubMed  CAS  Google Scholar 

  • Richardt, G., Federolf, G., and Habermann, E., 1985, The interaction of aluminum and other metal ions with calcium-calmodulin-dependent phosphodiesterase, Arch. Toxicol. 57:257–259.

    Article  PubMed  CAS  Google Scholar 

  • Rohn, T. T., Hinds, T. R., and Vincenzi, F. F., 1993, Ion transport ATPases as targets for free radical damage. Protection by an aminosteroid of the Ca2+ pump ATPase and Na+/K+ pump ATPase of human red blood cell membranes, Biochem. Pharmacol. 46:525–534.

    Article  PubMed  CAS  Google Scholar 

  • Rossi, M. A., Curzio, M., DiMauro, C., Fidale, F., Garramone, A., Esterbauer, H., Torrielli, M., and Dianzani, M. U., 1991, Experimental studies on the mechanism of action of 4-hydroxy-2,3-trans-nonenal, a lipid peroxidation product displaying chemotactic activity toward rat neutrophils, Cell Biochem. Funct. 9:163–170.

    Article  PubMed  CAS  Google Scholar 

  • Rothman, R. B., Reid, A., Mahboubi, A., Kim, C. H., De Costa, B. R., Jacobson, A. E., and Rice, K. C., 1991, Labeling by [3H]1,3-di(2-tolyl)guanidine of two high affinity binding sites in guinea pig brain: Evidence for allosteric regulation by calcium channel antagonists and pseudoallosteric modulation by sigma ligands, Mol. Pharmacol. 39:222–232.

    PubMed  CAS  Google Scholar 

  • Salmeron, A., Borroto, A., Fresno, M., Crumpton, M. J., Ley, S. C., and Alarcon, B., 1995, Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR ξ-chain, J. Immunol. 154:1675–1683.

    PubMed  CAS  Google Scholar 

  • Sanchez, C., Diaz-Nido, J., and Avila, J., 1995, Variations in in vivo phosphorylation at the proline-rich domain of the microtubule-associated protein 2 (MAP2) during rat brain development, Biochem. J. 306:481–487.

    PubMed  CAS  Google Scholar 

  • Schimke, I., Haberland, A., Will-Shahab, L., Kuttner, I., and Papies, B., 1992, In vitro effect of reactive 02 species on the β-receptor-adenylyl cyclase system, Mol. Cell. Biochem. 110:41–46.

    Article  PubMed  CAS  Google Scholar 

  • Schuman, E. M., Meffert, M. K., Schulman, H., and Madison, D. V, 1994, An ADP-ribosyltransferase as a potential target for nitric oxide action in hippocampal long-term potentiation, Proc. Natl. Acad. Sci. USA 91:11958–11962.

    Article  PubMed  CAS  Google Scholar 

  • Seki, K., Chen, H. C., and Huang, K. P., 1995, Dephosphorylation of protein kinase C substrates, neurogranin, neuromodulin, and MARCKS by calcineurin and protein phosphatases 1 and 2A, Arch. Biochem. Biophys. 316:673–679.

    Article  PubMed  CAS  Google Scholar 

  • Shao, Y, and McCarthy, K. D., 1993, Regulation of astroglial responsiveness to neuroligands in primary culture, Neuroscience 55:991–1001.

    Article  PubMed  CAS  Google Scholar 

  • Shiota, A., Hiramatsu, M., and Mori, A., 1989, Amino acid neurotransmitters in iron-induced epileptic foci of rats, Res. Commun. Chem. Pathol. Pharmacol. 66:123–133.

    PubMed  CAS  Google Scholar 

  • Shoham, S., Wertman, E., and Ebstein, R. P., 1992, Iron accumulation in the rat basal ganglia after excitatory amino acid injections—dissociation from neuronal loss, Exp. Neurol. 118:227–241.

    Article  PubMed  CAS  Google Scholar 

  • Sinosich, M. J., Davey, M. W., Teisner, B., and Grudzinskas, J. G., 1983, Comparative studies of pregnancy associated plasma protein-A and alpha 2-macroglobulin using metal chelate chromatography, Biochem. Int. 7:33–42.

    PubMed  CAS  Google Scholar 

  • Sirinathsinghji, D. J., Schuligoi, R., Heavens, R. P., Dixon, A., Iversen, S. D., and Hill, R. G., 1994, Temporal changes in the messenger RNS levels of cellular immediate early genes and neurotransmitter/receptor genes in the rat neostriatum and substantia nigra after acute treatment with eticlopride, a dopamine D2 receptor antagonist, Neuroscience 62:407–423.

    Article  PubMed  CAS  Google Scholar 

  • Sitaramayya, A., Marala, R. B., Hakki, S., and Sharma, R. K., 1991, aInteractions of nucleotide analogues with rod outer segment guanylate cyclase, Biochemistry 30:6742–6747.

    Article  PubMed  CAS  Google Scholar 

  • Smith, J. B., Smith, L., Pijuan, V., Zhuang, Y, and Chen, Y C., 1994, Transmembrane signals and protooncogene induction evoked by carcinogenic metals and prevented by zinc, Environ. Health Perspect. 102(Suppl 3): 181–189.

    PubMed  CAS  Google Scholar 

  • Stohs, S. J., and Bagchi, D., 1995, Oxidative mechanisms in the toxicity of metal ions, Free Radic. Biol. Med. 18:321–336.

    Article  PubMed  CAS  Google Scholar 

  • Swaiman, K. F., and Machen, V. L., 1985, The effect of iron on mammalian cortical neurons in culture, Neurochem. Res. 10:1261–1268.

    Article  PubMed  CAS  Google Scholar 

  • Swope, S. L., Moss, S. J., Blackstone, C. D., and Huganir, R. L., 1992, Phosphorylation of ligand-gated ion channels: A possible mode of synaptic plasticity, FASEB J. 6:2514–2523.

    PubMed  CAS  Google Scholar 

  • Taher, M. M., Garcia, J. G., and Natarajan, V, 1993, Hydroperoxide-induced diacylglycerol formation and protein kinase C activation in vascular endothelial cells, Arch. Biochem. Biophys. 303:260–266.

    Article  PubMed  CAS  Google Scholar 

  • Taneja, V, Mishra, K., and Agarwal, K. N., 1986, Effect of early iron deficiency in rat on the gamma-aminobutyric acid shunt in brain, J. Neurochem. 46:1670–1674.

    Article  PubMed  CAS  Google Scholar 

  • Tang, J., Rutishauser, U., and Landmesser, L., 1994, Polysialic acid regulates growth cone behavior during sorting of motor axons in the plexus region, Neuron. 13:405–414.

    Article  PubMed  CAS  Google Scholar 

  • Tian, W. N., and Deth, R. C., 1993, Precoupling of Gi/G(o)-linked receptors and its allosteric regulation by monovalent cations, Life Sci. 52:1899–1907.

    Article  PubMed  CAS  Google Scholar 

  • Tiffany-Castiglioni, E., Zmudzki, J., Wu, J. N., and Bratton, G. R., 1987, Effects of lead treatment on intracellular iron and copper concentrations in cultured astroglia, Metab. Brain Dis. 2:61–79.

    Article  PubMed  CAS  Google Scholar 

  • Tipper, J., Wollny, E., Fullilove, S., Kramer, G., and Hardesty, B., 1986, Interaction of the 56,000-dalton phosphoprotein from reticulocytes with regulin and inhibitor 2, J. Biol. Chem. 261:7144–7150.

    PubMed  CAS  Google Scholar 

  • Tomsig, J. L., and Suszkiw, J. B., 1993, Intracellular mechanism of Pb2+-induced norepinephrine release from bovine chromaffin cells, Am. J. Physiol. 265:C1630–6.

    Google Scholar 

  • Tsuji, Y, Miller, L. L., Miller, S. C., Torti, S. V, and Torti, F. M., 1991, Tumor necrosis factor-alpha and interleukin 1-alpha regulate transferrin receptor in human diploid fibroblasts. Relationship to the induction of ferritin heavy chain, J. Biol. Chem. 266:7257–7261.

    PubMed  CAS  Google Scholar 

  • Vartio, T., and Kuusela, P., 1991, Disulfide-bonded dimerization of fibronectin in vitro, Eur. J. Biochem. 202:597–604.

    Article  PubMed  CAS  Google Scholar 

  • Velez Pardo, C., Jimenez del Rio, M., Pinxteren, J., De Potter, W., Ebinger, G., and Vauquelin, G., 1995, Fe2+-mediated binding of serotonin and dopamine to skeletal muscle actin: resemblance to serotonin binding proteins, Eur. J. Pharmacol. 288:209–218.

    Article  PubMed  CAS  Google Scholar 

  • Vig, P. J., Ravi, K., and Nath, R., 1991, Interaction of metals with brain calmodulin purified from normal and cadmium exposed rats, Drug Chem. Toxicol. 14:207–218.

    Article  PubMed  CAS  Google Scholar 

  • Vincent, J. B., and Averill, B. A., 1990, Sequence homology between purple acid phosphatases and phosphoprotein phosphatases. Are phosphoprotein phosphatases metalloproteins containing oxide-bridged dinuclear metal centers? FEBS Lett. 263:265–268.

    Article  PubMed  CAS  Google Scholar 

  • Wade, R. S., and Castro, C. E., 1990, Redox reactivity of iron(III) porphyrins and heme proteins with nitric oxide. Nitrosyl transfer to carbon, oxygen, nitrogen, and sulfur, Chem. Res. Toxicol. 3:289–291.

    Article  PubMed  CAS  Google Scholar 

  • Waldmeier, P. C., Buchle, A. M., and Steulet, A. F., 1993, Inhibition of catechol-O-methyltransferase (COMT) as well as tyrosine and tryptophan hydroxylase by the orally active iron chelator, 1,2-dimethyl-3-hydroxypyridin-4-one (L1, CP20), in rat brain in vivo, Biochem. Pharmacol. 45:2417–2424.

    Article  PubMed  CAS  Google Scholar 

  • Wang, J., Rousseau, D. L., Abu-Soud, H. M., and Stuehr, D. J., 1994, Heme coordination of NO in NO synthase, Proc. Natl. Acad. Sci. USA 91:10512–10516.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L. Y, Taverna, F. A., Huang, X. P., MacDonald, J. F, and Hampson, D. R., 1993, Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase, Science 259:1173–1175.

    Article  PubMed  CAS  Google Scholar 

  • Winegar, B. D., and Lansman, J. B., 1991, Block of current through single calcium channels by Fe, Co, and Ni. Location of the transition metal binding site in the pore, J. Gen. Physiol. 97:351–367.

    Article  PubMed  CAS  Google Scholar 

  • Winrow, V. R., Winyard, P. G., Morris, C. J., and Blake, D. R., 1993, Free radicals in inflammation: Second messengers and mediators of tissue destruction, Br. Med. Bull. 49:506–522.

    PubMed  CAS  Google Scholar 

  • You, G. F., Buccigross, J. M., and Nelson, D. J., 1990, Comparison of Ca(II), Cd(II), and Mg(II) titration of tyrosine-99 spin-labeled bovine calmodulin, J. Inorg. Biochem. 38:117–125.

    Article  PubMed  CAS  Google Scholar 

  • Youdim, M. B. H., Ben-Shachar, D., and Yehuda, S., 1989, Putative biological mechanisms of the effect of iron deficiency on brain biochemistry and behavior, Am. J. Clin. Nutr. 50:607–617.

    PubMed  CAS  Google Scholar 

  • Yu, M. J., McCowan, J. R., Phebus, L. A., Towner, R. D., Ho, P. P., Keith, P. T, Luttman, C. A., Saunders, R. D., Ruterbories, K. J., and Lindstrom, T. D., 1993, Benzylamine antioxidants: Relationship between structure, peroxyl radical scavenging, lipid peroxidation inhibition, and cytoprotection, J. Med. Chem. 36:1262–1271.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, Y, Tatsuno, T., Carney, J. M., and Mattson, M. P., 1993, Basic FGF, NGF, and IGFs protect hippocampal and cortical neurons against iron-induced degeneration, J. Cereb. Blood Flow Metab. 13:378–388.

    Article  PubMed  Google Scholar 

  • Zhang, Z. H., Zuo, Q. H., and Wu, X. R., 1989, Effects of lipid peroxidation on GABA uptake and release in iron-induced seizures, Chin. Med. J. (Engl.) 102:24–27.

    CAS  Google Scholar 

  • Zorumski, C. F., and Thio, L. L., 1992, Properties of vertebrate glutamate receptors: Calcium mobilization and desensitization, Prog. Neurobiol. 39:295–336.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Pharmacology, Bruce Rappaport Family Research Institute, Faculty of Medicine, Technion, Haifa, 31096, Israel

    Yelena Glinka, Michael Gassen & Moussa B. H. Youdim

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  1. Yelena Glinka
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  2. Michael Gassen
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  1. Pennsylvania State University, Hershey, Pennsylvania, USA

    James R. Connor

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Glinka, Y., Gassen, M., Youdim, M.B.H. (1997). Iron and Neurotransmitter Function in the Brain. In: Connor, J.R. (eds) Metals and Oxidative Damage in Neurological Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0197-2_1

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