Abstract
Essential trace elements are commonly found in altered concentrations in the brains of patients with neurodegenerative diseases. Many studies in trace metal determination and quantification are conducted in tissue, cell culture or whole brain. In the present investigation, we determined by ICP-MS Fe, Cu, Zn, Ca, Se, Co, Cr, Mg, and Mn in organelles (mitochondria, nuclei) and whole motor neuron cell cultured in vitro. We performed experiments using two ways to access oxidative stress: cell treatments with H2O2 or Aβ-42 peptide in its oligomeric form. Both treatments caused accumulation of markers of oxidative stress, such as oxidized proteins and lipids, and alteration in DNA. Regarding trace elements, cells treated with H2O2 showed higher levels of Zn and lower levels of Ca in nuclei when compared to control cells with no oxidative treatments. On the other hand, cells treated with Aβ-42 peptide in its oligomeric form showed higher levels of Mg, Ca, Fe and Zn in nuclei when compared to control cells. These differences showed that metal flux in cell organelles during an intrinsic external oxidative condition (H2O2 treatment) are different from an intrinsic external neurodegenerative treatment.
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Ahmed M, Davis J, Aucoin D et al (2010) Structural conversion of neurotoxic amyloid-beta(1-42) oligomers to fibrils. Nat Struct Mol Biol 17:561–567. doi:10.1038/nsmb.1799
Alberdi E, Sánchez-Gómez MV, Cavaliere F et al (2010) Amyloid β oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium 47:264–272. doi:10.1016/j.ceca.2009.12.010
Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10(Suppl):S18–S25. doi:10.1038/nrn1434
Andrási E, Igaz S, Molnár ZMS (2000) Disturbances of magnesium concentrations in various brain areas in Alzheimer’s disease. Magnes Res 13:189–196
Armstrong RA, Winsper SJ, Blair JA (1995) Hypothesis: is Alzheimer’ s disease a metal-induced Immune Disorder? Neurodegeneration 4:107–111
Barnham KJ, Bush AI (2008) Metals in Alzheimer’s and Parkinson’s diseases. Curr Opin Chem Biol 12:222–228. doi:10.1016/j.cbpa.2008.02.019
Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214. doi:10.1038/nrd1330
Batista BL, Grotto D, Rodrigues JL et al (2009) Determination of trace elements in biological samples by inductively coupled plasma mass spectrometry with tetramethylammonium hydroxide solubilization at room temperature. Anal Chim Acta 646:23–29. doi:10.1016/j.aca.2009.05.022
Baum L, Chan IHS, Cheung SK-K et al (2010) Serum zinc is decreased in Alzheimer’s disease and serum arsenic correlates positively with cognitive ability. Biometals 23:173–179. doi:10.1007/s10534-009-9277-5
Berridge MJ (2010) Calcium hypothesis of Alzheimer’s disease. Eur J Physiol 459:441–449. doi:10.1007/s00424-009-0736-1
Berridge MJ, Bootman MD, Lipp P (1998) Calcium—a life and death signal. Nature 395:645–648. doi:10.1038/27094
Bertuchi FR, Bourgeon DMG, Landemberger MC et al (2012) PrP C displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrP C knockout mice. Biochem Biophys Res Commun 418:27–32. doi:10.1016/j.bbrc.2011.12.098
Bertuchi FR, Papai R, Ujevic M et al (2014) General chelating action of copper, zinc and iron in mammalian cells. Anal Methods 6:8488–8493. doi:10.1039/C4AY01912A
Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 31:454–463. doi:10.1016/j.tins.2008.06.005
Bleackley MR, Macgillivray RT (2011) Transition metal homeostasis: from yeast to human disease. Biometals 24:785–809. doi:10.1007/s10534-011-9451-4
Bourassa MW, Miller LM (2012) Metal imaging in neurodegenerative diseases. Metallomics 4:721–738. doi:10.1039/c2mt20052j
Campbell A, Smith mA, Sayre LM et al (2001) Mechanisms by which metals promote events connected to neurodegenerative diseases. Brain Res Bull 55:125–132
Cardoso B, Bush AI, Hare DJ (2015) Selenium, selenoproteins and neurodegenerative diseases. Metallomics 7:1213–1228. doi:10.1039/C5MT00075K
Cerchiaro G, Manieri TM, Bertuchi FR (2013) Analytical methods for copper, zinc and iron quantification in mammalian cells. Metallomics 5:1336–1345. doi:10.1039/c3mt00136a
Cheung Y-T, Lau WK-W, Yu M-S et al (2009) Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology 30:127–135. doi:10.1016/j.neuro.2008.11.001
Ciccotosto GD, James SA, Altissimo M et al (2014) redox active metals by X-ray fluorescence microscopy in cortical neurons derived from APP and APLP2 knockout tissue. Metallomics 6:1894–1904. doi:10.1039/C4MT00176A
Çillilier E, Ozturk S (2007) Serum magnesium level and clinical deterioration in Alzheimer disease. Gerontology 53:419–422. doi:10.1159/000110873
Claiborn A (1985) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press, Inc., Boca Raton
Cohen HJ, Brown MR, Hamilton D et al (1989) Glutathione peroxidase and selenium deficiency in patients receiving home parenteral nutrition: time course for development of deficiency and repletion of enzyme activity in plasma and blood cells. Am J Clin Nutr 49:132–139
Collins AR (2004) The comet assay for DNA damage and repair. Mol Biotechnol 26:249–261
Corrigan FM, Reynolds GP, Ward NI (1993) Hippocampal tin, aluminum and zinc in Alzheimer’s disease. Biometals 6:149–154
Demuro A, Mina E, Kayed R et al (2005) Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers. J Biol Chem 280:17294–17300. doi:10.1074/jbc.M500997200
Deshpande A, Mina E, Glabe C, Busciglio J (2006) Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J Neurosci 26:6011–6018. doi:10.1523/JNEUROSCI.1189-06.2006
Farina M, Avila DS, da Rocha JBT, Aschner M (2013) Metals, oxidative stress and neurodegeneration: a focus on iron, manganese and mercury. Neurochem Int 62:575–594. doi:10.1016/j.neuint.2012.12.006
Gaeta A, Hider RC (2005) The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. Br J Pharmacol 146:1041–1059. doi:10.1038/sj.bjp.0706416
Ganio K, James SA, Hare DJ et al (2016) Accurate biometal quantification per individual Caenorhabditis elegans. Analyst 141:1434–1439. doi:10.1039/C5AN02544C
Glabe CG (2006) Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging 27:570–575. doi:10.1016/j.neurobiolaging.2005.04.017
González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2014) Homeostasis of metals in the progression of Alzheimer’s disease. Biometals 27:539–549. doi:10.1007/s10534-014-9728-5
Grumolato L, Ghzili H, Montero-Hadjadje M et al (2008) Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+ mobilization and neuroendocrine secretion. FASEB J 22:1756–1768. doi:10.1096/fj.06-075820
Hadley H, Draperand M (1990) Malondial dehyde determination as index of lipid peroxidation. Assay Repair Biol Damage 186:421–431
Hare DJ, New EJ (2016) On the outside looking in: redefining the role of analytical chemistry in the biosciences. Chem Commun. doi:10.1039/C6CC00128A
Hare DJ, Arora M, Jenkins NL et al (2015) Is early-life iron exposure critical in neurodegeneration? Nat Rev Neurol. doi:10.1038/nrneurol.2015.100
Huang X, Moir RD, Tanzi RE et al (2004) Redox active metals, oxidative stress, and Alzheimer’s disease pathology. Ann New Acad Sci 1012:153–163. doi:10.1196/annals.1306.012
Jackman J, O’Connor PM (1998) Methods for synchronizing cells at specific. In: Bonifacino JS et al (eds) Current protocols in cell biology. Wiley, New York, pp 1–20
James SA, Volitakis I, Adlard PA et al (2012) Elevated labile Cu is associated with oxidative pathology in Alzheimer disease. Free Radic Biol Med 52:298–302. doi:10.1016/j.freeradbiomed.2011.10.446
Jomova K, Vondrakova D, Lawson M, Valko M (2010) Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem 345:91–104. doi:10.1007/s11010-010-0563-x
Ke Y, Qian ZM (2003) Iron misregulation in the brain: a primary cause of neurodegenerative disorders. Lancet Neurol 2:246–253. doi:10.1016/S1474-4422(03)00353-3
Kozlowski H, Luczkowski M, Remelli M, Valensin D (2012) Copper, zinc and iron in neurodegenerative diseases (Alzheimer’s, Parkinson’s and prion diseases). Coord Chem Rev 256:2129–2141. doi:10.1016/j.ccr.2012.03.013
Kryukov GV, Castellano S, Novoselov SV et al (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443. doi:10.1126/science.1083516
Lakshmi BVS, Sudhakar M, Prakash KS (2015) Protective effect of selenium against aluminum chloride-induced Alzheimer’s disease: behavioral and biochemical alterations in rats. Biol Trace Elem Res 165:67–74. doi:10.1007/s12011-015-0229-3
Lazzari C, Kipanyula MJ, Agostini M et al (2015) Aβ42 oligomers selectively disrupt neuronal calcium release. Neurobiol Aging 36:877–885. doi:10.1016/j.neurobiolaging.2014.10.020
Levine RL (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzimol 186:464–478
Lim GP, Chu T, Yang F et al (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370–8377
Litwin T, Gromadzka G, Szpak GM et al (2013) Brain metal accumulation in Wilson’s disease. J Neurol Sci 329:55–58. doi:10.1016/j.jns.2013.03.021
Lothian A, Hare DJ, Grimm R et al (2013) Metalloproteomics: principles, challenges and applications to neurodegeneration. Front Aging Neurosci 5:1–7. doi:10.3389/fnagi.2013.00035
Matias AC, Manieri TM, Cipriano SS et al (2013) Diethyldithiocarbamate induces apoptosis in neuroblastoma cells by raising the intracellular copper level, triggering cytochrome c release and caspase activation. Toxicol In Vitro 27:349–357. doi:10.1016/j.tiv.2012.08.017
Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639. doi:10.1038/nature02621
Mattson MP (2007) Calcium and neurodegeneration. Aging Cell 6:337–350. doi:10.1111/j.1474-9726.2007.00275.x
Maynard CJ, Bush AI, Masters CL et al (2005) Metals and amyloid-beta in Alzheimer’s disease. Int J Exp Pathol 86:147–159. doi:10.1111/j.0959-9673.2005.00434.x
Mohd-Taufek N, Cartwright D, Davies M et al (2016) The simultaneous analysis of eight essential trace elements in human milk by ICP-MS. Food Anal Methods 1–8: doi:10.1007/s12161-015-0396-z
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. doi:10.1016/0022-1759(83)90303-4
Mukherjee A, Swarnakar S (2015) Implication of matrix metalloproteinases in regulating neuronal disorder. Mol Biol Rep 42:1–11. doi:10.1007/s11033-014-3752-y
Nackerdien Z, Kasprzak KS, Rao G et al (1991) Nickel(II) - and cobalt(II) -dependent damage by hydrogen peroxide to the dna bases in isolated human chromatin nickel (H)- and cobalt (II)-dependent damage by hydrogen peroxide to the DNA bases in isolated human chromatin. Cancer Res 51:5837–5842
Nadin SB, Vargas-Roig LM, Ciocca DR (2001) A silver staining method for single-cell gel assay. J Histochem Cytochem 49:1183–1186. doi:10.1177/002215540104900912
Nuttall JR, Oteiza PI (2014) Zinc and the aging brain. Genes Nutr 9:1–11. doi:10.1007/s12263-013-0379-x
Olivieri G, Hess C, Savaskan E et al (2001) Melatonin protects SHSY5Y neuroblastoma cells from cobalt-induced oxidative stress, neurotoxicity and increased beta-amyloid secretion. J Pineal Res 31:320–325
Poersch A, dos Santos FV, Maciel MAM et al (2007) Protective effect of DCTN (trans-dehydrocrotonin) against induction of micronuclei and apoptosis by different mutagenic agents in vitro. Mutat Res 629:14–23. doi:10.1016/j.mrgentox.2007.01.001
Popescu BFG, Nichol H (2011) Mapping brain metals to evaluate therapies for neurodegenerative disease. CNS Neurosci Ther 17:256–268. doi:10.1111/j.1755-5949.2010.00149.x
Raff MC, Whitmore AV, Finn JT (2002) Axonal self-destruction and neurodegeneration. Science 296:868–871. doi:10.1126/science.1068613
Rana SVS (2008) Metals and apoptosis: recent developments. J Trace Elem Med Biol 22:262–284. doi:10.1016/j.jtemb.2008.08.002
Reeves MA, Bellinger FP, Berry MJ (2010) The neuroprotective functions of selenoprotein M and its role in cytosolic calcium regulation. Antioxid Redox Signal 12:809–818. doi:10.1089/ars.2009.2883
Reilly CA, Steven DA (2001) Measurement of lipid peroxidation. In: Eaton DL, Kavanagh TJ (eds) Current protocols in toxicology. Wiley, New York, pp 1–13
Rembach A, Hare DJ, Lind M et al (2013) Decreased copper in Alzheimer disease brain is predominantly in the soluble extractable fraction. Int J Alzheimers Dis 2013:1–7. doi:10.1155/2013/623241
Rembach A, Hare DJ, Doecke JD et al (2014) Decreased serum zinc is an effect of ageing and not Alzheimer’s disease. Metallomics 6:1216–1219. doi:10.1039/c4mt00060a
Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl. Methods Enzymol Enzym 233:357–363
Rita Cardoso B, Silva Bandeira V, Jacob-Filho W, Franciscato Cozzolino SM (2014) Selenium status in elderly: relation to cognitive decline. J Trace Elem Med Biol 28:422–426. doi:10.1016/j.jtemb.2014.08.009
Roveri A, Coassin M, Maiorino M et al (1992) Effect of hydrogen peroxide on calcium homeostasis in smooth muscle cells. Arch Biochem Biophys 297:265–270
Schrag M, Mueller C, Oyoyo U et al (2011) Iron, zinc and copper in the Alzheimer’s disease brain: a quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion. Prog Neurobiol 94:296–306. doi:10.1016/j.pneurobio.2011.05.001
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191. doi:10.1016/0014-4827(88)90265-0
Sjögren M, Davidsson P, Tullberg M et al (2001) Both total and phosphorylated tau are increased in Alzheimer’s disease. Neurol Neurosurg Psychiatry 70:624–630
Smorgon C, Mari E, Atti A (2004) Trace elements and cognitive impairment: an elderly cohort study. Arch Gerontol Geriatr Suppl 9:393–402. doi:10.1016/j.archger.2004.04.050
Socha MJ, Boerman EM, Behringer EJ et al (2015) Advanced age protects microvascular endothelium from aberrant Ca2+ influx and cell death induced by hydrogen peroxide. J Physiol 593:2155–2169. doi:10.1113/JP270169
Sparks DL, Friedland R, Petanceska S et al (2006) Trace copper levels in the drinking water, but not zinc or aluminum influence CNS Alzheimer-like pathology. J Nutr Heal Aging 10:247–254
Stine WB, Dahlgren KN, Krafft GA, LaDu MJ (2003) In vitro characterization of conditions for amyloid-beta peptide oligomerization and fibrillogenesis. J Biol Chem 278:11612–11622. doi:10.1074/jbc.M210207200
Strober W (2001) Trypan blue exclusion test of cell viability. In: Coligan JE et al (eds) Current protocols in immunology. Wiley, Hoboken
Suleiman JS, Hu B, Pu X et al (2007) Nanometer-sized zirconium dioxide microcolumn separation/preconcentration of trace metals and their determination by ICP-OES in environmental and biological samples. Microchim Acta 159:379–385. doi:10.1007/s00604-007-0742-y
Tice RR, Agurell E, Anderson D et al (2000) Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 35:206–221
Timmons MD, Bradley MA, Lovell MA, Lynn BC (2011) Procedure for the isolation of mitochondria, cytosolic and nuclear material from a single piece of neurological tissue for high-throughput mass spectral analysis. J Neurosci Methods 197:279–282. doi:10.1016/j.jneumeth.2011.02.027
Tsang CK, Liu Y, Thomas J et al (2014) Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat Commun 5:3446. doi:10.1038/ncomms4446
Tüzen M (2003) Determination of heavy metals in fish samples of the middle Black Sea (Turkey) by graphite furnace atomic absorption spectrometry. Food Chem 80:119–123. doi:10.1016/S0308-8146(02)00264-9
Valko M, Rhodes CJ, Moncol J et al (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40. doi:10.1016/j.cbi.2005.12.009
Wei W, Zhang C, Liu AL et al (2009) PCB126 enhanced the genotoxicity of BaP in HepG2 cells by modulating metabolic enzyme and DNA repair activities. Toxicol Lett 189:91–95. doi:10.1016/j.toxlet.2009.03.009
Yevier E, Deibel MA, Ehmann WD, Markesbery WR (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress. J Neurol Sci 143:137–142
Yu J, Sun M, Chen Z et al (2010) Magnesium modulates amyloid-beta protein precursor trafficking and processing. J Alzheimer’s Dis 20:1091–1106. doi:10.3233/JAD-2010-091444
Zheng W, Monnot AD (2012) Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases. Pharmacol Ther 133:177–188. doi:10.1016/j.pharmthera.2011.10.006
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The authors acknowledge FAPESP (São Paulo Research Foundation, process 2016/09652-9), CAPES and CNPq.
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Lago, L., Nunes, E.A., Vigato, A.A. et al. Flow of essential elements in subcellular fractions during oxidative stress. Biometals 30, 83–96 (2017). https://doi.org/10.1007/s10534-016-9988-3
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DOI: https://doi.org/10.1007/s10534-016-9988-3