Role of Zinc in nervous system cells
More details
Hide details
Independent Laboratory for Cell Metabolism, Institute of Rural Health, Lublin, Poland
J Pre Clin Clin Res. 2011;5(1):12–15
Zinc has been identified as one of the most important minerals in the human body. As a trace element, zinc (Zn) is vital for the growth and development of an organism. Its basic functioning centres around its involvement in the structure of macro-elementary compounds, and the activation of numerous enzymes engaged in the metabolic processes. In the organic world, over 300 zinc-dependent enzymes have been identified. Our bodies need zinc to make insulin and eliminate toxins, and zinc is also important for the anti-oxidant maintenance and maintaining a healthy immune system. Laboratory experiments appeared discharged its ant-oxidant functions. The first is that dozens of vital enzymes within the body contain zinc, and in these enzymes the zinc molecule acts directly as an anti-oxidant, protecting the biochemical structure of the enzyme from free radical attack. Secondly, zinc acts to stabilize protein which may otherwise react with highly unstable minerals, particularly iron and copper, to form free radicals. Furthermore, zinc plays a very important role in normal brain development and function. In growing organisms, zinc is known to be indispensable for the undisturbed formation of their nervous systems. In adults, zinc deficiency results in behavioral symptoms, such as memory problems, malaise, or higher susceptibility to stress. On the other hand, it is believed that an excess of free zinc is detrimental and can lead to neuronal death. Studies confirm that the toxicity of zinc shows up when there is an increase in the third fraction or free zinc in a cell (pool of zinc, so called ‘free” zinc, which is not bound to proteins). The neurotoxicity of zinc has been demonstrated on animal models in which a stroke, ischemia, Alzheimer’s disease, or convulsions were induced. The detailed mechanism of the toxic activity of zinc is not known, but it seems that the main cause of neuronal death is low energy production by mitochondria.
Frassinetti S, Bronzetti G, Caltavuturo L, Cini M, Croce CD. Th e role of zinc in life: a review. J Environ Pathol Toxicol Oncol 2006;25:597- 610.
Zhang Y, Aizenman E, DeFranco DB, Rosenberg P. Intracellular zinc release, 12-lipoxygenase activation and MAPK dependent neuronal and oligodendrioglial death. Mol Med 2007;13:350-355.
Jia D, Jeng J, Sensi SL, Weiss JH. Zn2+ currents are mediated by calciumpermeable AMPA/kainate channels in cultured murine hippocampal neurones. J Physiol (Lond) 2002;543:35-48.
Suemori S, Shimazawa M, Kawase K, Satoh M, Nagase H, Yamamoto T, Hara H. Metallothionein, an endogenous antioxidant, protects against retinal neuron damage in mice. Invest Ophtalmol Vis Sci 2006;47:3975- 3982.
Wang K, Zhou B, Kuo YM, Zemansky J, Gitschier J. A novel number of zinc transporter family is defective in acrodermatitis enteropathica. Am J Hum Genet 2002;71:66-73.
Colvin RA, Fontaine CP, Laskowski M, Th omas D. Zn2+ transporters and Zn2+ homeostasis in neurons. Eur J Pharmacol 2003;479:171-185.
Floriańczyk B, Osuchowski J, Kaczmarczyk R, Trojanowski T, Stryjecka- Zimmer M. Infl uence of metallothioneins on zinc and copper distribution in brain tumours. Folia Neuropathol 2003;41:11-14.
Sensi SL, Jeng JM. Rethinking the excitotoxic ionic milleu: the emerging role of Zn(2+) in ishemic neuronal injury. Curr Mol Med 2004;4:87- 111.
Burdette SC, Lippard SJ. Meeting of the minds: metalloneurochemistry. Proc Natl Acad Sci USA 2003;100:3605-3610.
Th irumoorthy N, Manisenthil Kumar KT, Shyam Sundar A, Panayappan L, Chatterjee M. Metallothionein: An overview. World J Gastroenterol 2007;21:993-996.
Lene BK, Berezin V, Bock E, Penkowa M. Th e role of metallothionein II in neuronal diff erentiation and survival. Brain Res 2003;28:128-136.
Takeda A: Movement of zinc and its functional signifi cance in the brain. Brain Res Rev 2000;34:137-148.
Canzoniero LM, Turetsky DM, Choi DW. Measurement of intracellular free zinc concentrations accompanying zinc- induced neuronal death. J Neurosci 1999;19:1–6.
Th ompson RB., Peterson D, Mahoney W, Cramer M, Maliwal BP, Suh SW, Frederickson C, Fierke C, Herman P. Fluorescent zinc indicators for neurobiology. J Neorosci Methods 2002;118:63-75.
Frederickson CJ. Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol 1989;31:145–238.
Qian J, Noebels JL. Exocytosis of vesicular zinc reveals persistent depresion of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse. J Neurosci 2006;26:6089-6095.
Cole TB, Wenzel HJ, Kafer KE, Schwartzkroin PA, Palmiter RD. Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci USA 1999;46:1716-1721.
Rapizzi E, Pinton P, Szabadkai G, Więckowski MR, Vandecasteele G, Baird G, Tuft RA, Fogarty KE, Rizzuto R. Recombinant expression of the voltage-deprendent anion channel enhances the transfer of Ca microdomains to mitochondria. J Cell Biol 2002;159:613-624.
Vogt K, Mellor J, Tong G, Nicoll R. Th e action of synaptically released zinc at hippocampal mossy fi ber synapses. Neoron 2000;26:187-196.
Hsiao B, Mihalak KB, Magleby KL, Charles W, Luetje CW. Zinc potentiates neuronal nicotinic receptors by increasing burst duration. J Neurophysiol 2008;99:999–1007.
Li Y, Hough CJ, Frederickson CJ, Sarvey JM. Induction of mossy fi ber CA3 long-term potentiation requires translocation of synaptically released Zn2+. J. Neurosci 2001;21:8015-8025.
Smart TG, Hosie AM, Miller PS. Zn2+ Ions: modulators of excitatory and inhibitory synaptic activity. Neuroscientist 2004;10:432-442.
Choi DW, Koh JY. Zinc and brain injury. Annu Rev Neurosci 1998;21:347–375.
Cuajungco MP, Lees GJ. Zinc metabolism in the brain: relevance to human neurodegenerative disorders. Neurobiol Dis 1997;4:137–169.
Levenson CW. Trace metal regulation of neuronal apoptosis: From genes to behavior. Physiol Behavior 2005;15:399-406.
Weiss JH, Sensi SL, Koh JY. Zn(2+) a novel ionic mediator of neural injury in brain disease. Trends Pharmacol Sci 2000;21:395-401.
Jacobs P, Wood L. Zinc. Disease-a-Month 2003;49:601-608.
Doran B, Gherbesi N, Hendricks G, Flavell RA, Davis R, Gangwani L. Efi ciency of the zinc fi nger protein ZPR1 causes neurodegeration. Proc Natl Acad Sci USA 2006;103:7471-7475.
Endo H, Nito C, Kamada H, Nishi T, Chan PH. Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons aft er transient global cerebral ischemia in rats. J Cereb Blood Flow Metab 2006;26:1479-1489.
Religa D, Strozyk D, Cherny RA, Volitakis I, Haroutunian V, Winblad B, Naslund J, Bush AI. Elevated cortical zinc in Alzheimer disease. Neurology 2006;67:69-75.
Frederickson CJ, Koh JY, Bush AL. Th e neurobiology of zinc in health and disease. Nat Rev Neurosci 2005;6:449-462.
Floriańczyk B., Trojanowski T. Inhibition of respiratory processes by overbundance of zinc in neuronal cells. Folia Neuropath 2009;47:234- 239.
Kim J, Kim T-Y, Hwang JJ, Lee JY, Shin J-H, Byung Joo Gwag BJ, Koh J-Y. Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice. Neurobiology 2009;34:221- 229.
Qian J, Noebels JN. Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3–CA1 synapse. J Neuroscience 2006;26(22):6089–6095.
Malaiyandi LM. Interaction between zinc and mitochondria in neuronal injury. University of Pitsburgh 2005:152-154.
Ye B, Maret W, Vallee BL. Zinc metallthionein imported into liver mitochondria modulates respiration. Proc Natl Acad Sci USA 2001;98:2317- 2322.
Dineley KE, Votyakova TV, Reynolds IJ. Zinc inhibition of cellular energy production: implication for mitochondria and neurodegeneration. J Neurochem 2003;85:563-570.