Skip to main content

Advertisement

SpringerLink
Log in

Handling of Copper and Copper Oxide Nanoparticles by Astrocytes

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Copper is an essential trace element for many important cellular functions. However, excess of copper can impair cellular functions by copper-induced oxidative stress. In brain, astrocytes are considered to play a prominent role in the copper homeostasis. In this short review we summarise the current knowledge on the molecular mechanisms which are involved in the handling of copper by astrocytes. Cultured astrocytes efficiently take up copper ions predominantly by the copper transporter Ctr1 and the divalent metal transporter DMT1. In addition, copper oxide nanoparticles are rapidly accumulated by astrocytes via endocytosis. Cultured astrocytes tolerate moderate increases in intracellular copper contents very well. However, if a given threshold of cellular copper content is exceeded after exposure to copper, accelerated production of reactive oxygen species and compromised cell viability are observed. Upon exposure to sub-toxic concentrations of copper ions or copper oxide nanoparticles, astrocytes increase their copper storage capacity by upregulating the cellular contents of glutathione and metallothioneins. In addition, cultured astrocytes have the capacity to export copper ions which is likely to involve the copper ATPase 7A. The ability of astrocytes to efficiently accumulate, store and export copper ions suggests that astrocytes have a key role in the distribution of copper in brain. Impairment of this astrocytic function may be involved in diseases which are connected with disturbances in brain copper metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Liu J, Chakraborty S, Hosseinzadeh P, Yu Y, Tian S, Petrik I, Bhagi A, Lu Y (2014) Metalloproteins containing cytochrome, iron-sulfur, or copper redox centers. Chem Rev 114:4366–4469

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Scheiber IF, Dringen R (2013) Astrocyte functions in the copper homeostasis of the brain. Neurochem Int 62:556–565

    Article  PubMed  CAS  Google Scholar 

  3. Scheiber IF, Mercer JF, Dringen R (2014) Metabolism and functions of copper in brain. Prog Neurobiol 116:33–57

    Article  PubMed  CAS  Google Scholar 

  4. Gulec S, Collins JF (2014) Molecular mediators governing iron-copper interactions. Annu Rev Nutr 34:95–116

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Lovejoy DB, Guillemin GJ (2014) The potential for transition metal-mediated neurodegeneration in amyotrophic lateral sclerosis. Front Aging Neurosci 6:173

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87

    Article  PubMed  CAS  Google Scholar 

  7. Romero A, Ramos E, de Los Rios C, Egea J, Del Pino J, Reiter RJ (2014) A review of metal-catalyzed molecular damage: protection by melatonin. J Pineal Res 56:343–370

    Article  PubMed  CAS  Google Scholar 

  8. Allen NJ (2014) Astrocyte regulation of synaptic behavior. Annu Rev Cell Dev Biol 30:439–463

    Article  PubMed  CAS  Google Scholar 

  9. Haydon PG, Nedergaard M (2015) How do astrocytes participate in neural plasticity? Cold Spring Harb Perspect Biol 7:a020438

    Article  Google Scholar 

  10. Kaczor P, Rakus D, Mozrzymas JW (2015) Neuron-astrocyte interaction enhance GABAergic synaptic transmission in a manner dependent on key metabolic enzymes. Front Cell Neurosci 9:120

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rossi D (2015) Astrocyte physiopathology: at the crossroads of intercellular networking, inflammation and cell death. Prog Neurobiol 130:86–120

    Article  PubMed  CAS  Google Scholar 

  12. Verkhratsky A, Nedergaard M, Hertz L (2015) Why are astrocytes important? Neurochem Res 40:389–401

    Article  PubMed  CAS  Google Scholar 

  13. Brekke E, Morken TS, Sonnewald U (2015) Glucose metabolism and astrocyte-neuron interactions in the neonatal brain. Neurochem Int 82:33–41

    Article  PubMed  CAS  Google Scholar 

  14. Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35

    Article  PubMed  PubMed Central  Google Scholar 

  15. Butt AM, Fern RF, Matute C (2014) Neurotransmitter signaling in white matter. Glia 62:1762–1779

    Article  PubMed  Google Scholar 

  16. Dringen R, Brandmann M, Hohnholt MC, Blumrich EM (2015) Glutathione-dependent detoxification processes in astrocytes. Neurochem Res. doi:10.1007/s11064-014-1481-1

    Google Scholar 

  17. Dringen R, Spiller S, Neumann S, Koehler Y (2015) Uptake, metabolic effects and toxicity of arsenate and arsenite in astrocytes. Neurochem Res. doi:10.1007/s11064-015-1570-9

    Google Scholar 

  18. Rodriguez-Arellano JJ, Parpura V, Zorec R, Verkhratsky A (2015) Astrocytes in physiological aging and Alzheimer’s disease. Neuroscience. doi:10.1016/j.neuroscience.2015.01.007

    PubMed  Google Scholar 

  19. Verkhratsky A, Parpura V (2015) Astrogliopathology in neurological, neurodevelopmental and psychiatric disorders. Neurobiol Dis. doi:10.1016/j.nbd.2015.03.025

    PubMed  Google Scholar 

  20. Kodama H (1993) Recent developments in Menkes disease. J Inherit Metab Dis 16:791–799

    Article  PubMed  CAS  Google Scholar 

  21. Kodama H, Meguro Y, Abe T, Rayner MH, Suzuki KT, Kobayashi S, Nishimura M (1991) Genetic expression of Menkes disease in cultured astrocytes of the macular mouse. J Inherit Metab Dis 14:896–901

    Article  PubMed  CAS  Google Scholar 

  22. Szerdahelyi P, Kasa P (1986) Histochemical demonstration of copper in normal rat brain and spinal cord. Evidence of localization in glial cells. Histochemistry 85:341–347

    Article  PubMed  CAS  Google Scholar 

  23. Haywood S, Paris J, Ryvar R, Botteron C (2008) Brain copper elevation and neurological changes in north ronaldsay sheep: a model for neurodegenerative disease? J Comp Pathol 139:252–255

    Article  PubMed  CAS  Google Scholar 

  24. Bulcke F, Thiel K, Dringen R (2014) Uptake and toxicity of copper oxide nanoparticles in cultured primary brain astrocytes. Nanotoxicology 8:775–785

    PubMed  CAS  Google Scholar 

  25. Hare DJ, Grubman A, Ryan TM, Lothian A, Liddell JR, Grimm R, Matsuda T, Doble PA, Cherny RA, Bush AI, White AR, Masters CL, Roberts BR (2013) Profiling the iron, copper and zinc content in primary neuron and astrocyte cultures by rapid online quantitative size exclusion chromatography-inductively coupled plasma-mass spectrometry. Metallomics 5:1656–1662

    Article  PubMed  CAS  Google Scholar 

  26. Scheiber IF, Mercer JF, Dringen R (2010) Copper accumulation by cultured astrocytes. Neurochem Int 56:451–460

    Article  PubMed  CAS  Google Scholar 

  27. Scheiber IF, Schmidt MM, Dringen R (2010) Zinc prevents the copper-induced damage of cultured astrocytes. Neurochem Int 57:314–322

    Article  PubMed  CAS  Google Scholar 

  28. Scheiber IF, Dringen R (2011) Copper-treatment increases the cellular GSH content and accelerates GSH export from cultured rat astrocytes. Neurosci Lett 498:42–46

    Article  PubMed  CAS  Google Scholar 

  29. Scheiber IF, Dringen R (2011) Copper accelerates glycolytic flux in cultured astrocytes. Neurochem Res 36:894–903

    Article  PubMed  CAS  Google Scholar 

  30. Scheiber IF, Schmidt MM, Dringen R (2012) Copper export from cultured astrocytes. Neurochem Int 60:292–300

    Article  PubMed  CAS  Google Scholar 

  31. Qian Y, Zheng Y, Taylor R, Tiffany-Castiglioni E (2012) Involvement of the molecular chaperone Hspa5 in copper homeostasis in astrocytes. Brain Res 1447:9–19

    Article  PubMed  CAS  Google Scholar 

  32. Bulcke F, Santofimia-Castano P, Gonzalez-Mateos A, Dringen R (2015) Modulation of copper accumulation and copper-induced toxicity by antioxidants and copper chelators in cultured primary brain astrocytes. J Trace Elem Med Biol 32:168–176

    Article  PubMed  CAS  Google Scholar 

  33. Bulcke F, Dringen R (2015) Copper oxide nanoparticles stimulate glycolytic flux and increase the cellular contents of glutathione and metallothioneins in cultured astrocytes. Neurochem Res 40:15–26

    Article  PubMed  CAS  Google Scholar 

  34. Evans P, Matsunaga H, Kiguchi M (2008) Large-scale application of nanotechnology for wood protection. Nat Nanotechnol 3:577

    Article  PubMed  CAS  Google Scholar 

  35. Hanagata N, Zhuang F, Connolly S, Li J, Ogawa N, Xu M (2011) Molecular responses of human lung epithelial cells to the toxicity of copper oxide nanoparticles inferred from whole genome expression analysis. ACS Nano 5:9326–9338

    Article  PubMed  CAS  Google Scholar 

  36. Li CW, Ciston J, Kanan MW (2014) Electroreduction of carbon monoxide to liquid fuel on oxide-derived nanocrystalline copper. Nature 508:504–507

    Article  PubMed  CAS  Google Scholar 

  37. Patil PR, Krishnamurthy VN, Joshi SS (2008) Effect of nano-copper oxide and copper chromite on the thermal decomposition of ammonium perchlorate. Propellants Explos Pyrotech 33:266–270

    Article  CAS  Google Scholar 

  38. Rubilar O, Rai M, Tortella G, Diez MC, Seabra AB, Duran N (2013) Biogenic nanoparticles: copper, copper oxides, copper sulphides, complex copper nanostructures and their applications. Biotechnol Lett 35:1365–1375

    Article  PubMed  CAS  Google Scholar 

  39. Ahmad Z, Vargas-Reus MA, Bakhshi R, Ryan F, Ren GG, Oktar F, Allaker RP (2012) Antimicrobial properties of electrically formed elastomeric polyurethane-copper oxide nanocomposites for medical and dental applications. Methods Enzymol 509:87–99

    Article  PubMed  CAS  Google Scholar 

  40. Ben-Sasson M, Zodrow KR, Genggeng Q, Kang Y, Giannelis EP, Elimelech M (2014) Surface functionalization of thin-film composite membranes with copper nanoparticles for antimicrobial surface properties. Environ Sci Technol 48:384–393

    Article  PubMed  CAS  Google Scholar 

  41. Dankovich TA, Smith JA (2014) Incorporation of copper nanoparticles into paper for point-of-use water purification. Water Res 63:245–251

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Xu J, Li Z, Xu P, Xiao L, Yang Z (2013) Nanosized copper oxide induces apoptosis through oxidative stress in podocytes. Arch Toxicol 87:1067–1073

    Article  PubMed  CAS  Google Scholar 

  43. Karlsson HL, Cronholm P, Gustafsson J, Moller L (2008) Copper oxide nanoparticles are highly toxic: a comparison between metal oxide nanoparticles and carbon nanotubes. Chem Res Toxicol 21:1726–1732

    Article  PubMed  CAS  Google Scholar 

  44. Oberdorster G, Oberdorster E, Oberdorster J (2005) Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 113:823–839

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Balkhyour MA, Goknil MK (2010) Total fume and metal concentrations during welding in selected factories in Jeddah, Saudi Arabia. Int J Environ Res Public Health 7:2978–2987

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Szymczak W, Menzel N, Keck L (2007) Emission of ultrafine copper particles by universal motors controlled by phase angle modulation. J Aerosol Sci 38:520–531

    Article  CAS  Google Scholar 

  47. Kreyling WG, Semmler M, Erbe F, Mayer P, Takenaka S, Schulz H, Oberdorster G, Ziesenis A (2002) Translocation of ultrafine insoluble iridium particles from lung epithelium to extrapulmonary organs is size dependent but very low. J Toxicol Environ Health A 65:1513–1530

    Article  PubMed  CAS  Google Scholar 

  48. Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C (2004) Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:437–445

    Article  PubMed  CAS  Google Scholar 

  49. Sharma HS, Sharma A (2012) Neurotoxicity of engineered nanoparticles from metals. CNS Neurol Disord Drug Targets 11:65–80

    Article  PubMed  CAS  Google Scholar 

  50. Yim YS, Choi JS, Kim GT, Kim CH, Shin TH, Kim DG, Cheon J (2012) A facile approach for the delivery of inorganic nanoparticles into the brain by passing through the blood-brain barrier (BBB). Chem Commun (Camb) 48:61–63

    Article  CAS  Google Scholar 

  51. Gromnicova R, Davies HA, Sreekanthreddy P, Romero IA, Lund T, Roitt IM, Phillips JB, Male DK (2013) Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro. PLoS ONE 8:e81043

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. An L, Liu S, Yang Z, Zhang T (2012) Cognitive impairment in rats induced by nano-CuO and its possible mechanisms. Toxicol Lett 213:220–227

    Article  PubMed  CAS  Google Scholar 

  53. Haywood S, Vaillant C (2014) Overexpression of copper transporter CTR1 in the brain barrier of North Ronaldsay sheep: implications for the study of neurodegenerative disease. J Comp Pathol 150:216–224

    Article  PubMed  CAS  Google Scholar 

  54. Brown DR (2004) Role of the prion protein in copper turnover in astrocytes. Neurobiol Dis 15:534–543

    Article  PubMed  CAS  Google Scholar 

  55. Eisses JF, Chi Y, Kaplan JH (2005) Stable plasma membrane levels of hCTR1 mediate cellular copper uptake. J Biol Chem 280:9635–9639

    Article  PubMed  CAS  Google Scholar 

  56. Eisses JF, Kaplan JH (2002) Molecular characterization of hCTR1, the human copper uptake protein. J Biol Chem 277:29162–29171

    Article  PubMed  CAS  Google Scholar 

  57. Lee J, Petris MJ, Thiele DJ (2002) Characterization of mouse embryonic cells deficient in the ctr1 high affinity copper transporter. Identification of a Ctr1-independent copper transport system. J Biol Chem 277:40253–40259

    Article  PubMed  CAS  Google Scholar 

  58. Qian Y, Tiffany-Castiglioni E (2003) Lead-induced endoplasmic reticulum (ER) stress responses in the nervous system. Neurochem Res 28:153–162

    Article  PubMed  CAS  Google Scholar 

  59. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488

    Article  PubMed  CAS  Google Scholar 

  60. Jeong SY, David S (2003) Glycosylphosphatidylinositol-anchored ceruloplasmin is required for iron efflux from cells in the central nervous system. J Biol Chem 278:27144–27148

    Article  PubMed  CAS  Google Scholar 

  61. Urrutia P, Aguirre P, Esparza A, Tapia V, Mena NP, Arredondo M, Gonzalez-Billault C, Nunez MT (2013) Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem 126:541–549

    Article  PubMed  CAS  Google Scholar 

  62. Burdo JR, Menzies SL, Simpson IA, Garrick LM, Garrick MD, Dolan KG, Haile DJ, Beard JL, Connor JR (2001) Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. J Neurosci Res 66:1198–1207

    Article  PubMed  CAS  Google Scholar 

  63. Brown LR, Harris DA (2003) Copper and zinc cause delivery of the prion protein from the plasma membrane to a subset of early endosomes and the Golgi. J Neurochem 87:353–363

    Article  PubMed  CAS  Google Scholar 

  64. Pauly PC, Harris DA (1998) Copper stimulates endocytosis of the prion protein. J Biol Chem 273:33107–33110

    Article  PubMed  CAS  Google Scholar 

  65. Arredondo M, Munoz P, Mura CV, Nunez MT (2003) DMT1, a physiologically relevant apical Cu1+ transporter of intestinal cells. Am J Physiol Cell Physiol 284:C1525–C1530

    Article  PubMed  CAS  Google Scholar 

  66. Tulpule K, Robinson SR, Bishop GM, Dringen R (2010) Uptake of ferrous iron by cultured rat astrocytes. J Neurosci Res 88:563–571

    PubMed  CAS  Google Scholar 

  67. Gomes IM, Maia CJ, Santos CR (2012) STEAP proteins: from structure to applications in cancer therapy. Mol Cancer Res 10:573–587

    Article  PubMed  CAS  Google Scholar 

  68. Ohgami RS, Campagna DR, McDonald A, Fleming MD (2006) The steap proteins are metalloreductases. Blood 108:1388–1394

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Zhang Y, Chen K, Sloan SA, Bennett ML, Scholze AR, O’Keeffe S, Phatnani HP, Guarnieri P, Caneda C, Ruderisch N, Deng S, Liddelow SA, Zhang C, Daneman R, Maniatis T, Barres BA, Wu JQ (2014) An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 34:11929–11947

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Harrison FE, May JM (2009) Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med 46:719–730

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Rice ME (2012) Brain ascorbate: protective, yet permissive for redox signaling. In: Choi I-J, Gruetter R (eds) Advances in neurobiology 4: neural metabolism in vivo. Springer, Heidelberg, pp 1051–1073

    Chapter  Google Scholar 

  72. Lane DJ, Lawen A (2013) The glutamate aspartate transporter (GLAST) mediates L-glutamate-stimulated ascorbate-release via swelling-activated anion channels in cultured neonatal rodent astrocytes. Cell Biochem Biophys 65:107–119

    Article  PubMed  CAS  Google Scholar 

  73. Wilson JX, Peters CE, Sitar SM, Daoust P, Gelb AW (2000) Glutamate stimulates ascorbate transport by astrocytes. Brain Res 858:61–66

    Article  PubMed  CAS  Google Scholar 

  74. Geppert M, Petters C, Thiel K, Dringen R (2013) The presence of serum alters the properties of iron oxide nanoparticles and lowers their accumulation by cultured brain astrocytes. J Nanopart Res 15:1–15

    Article  CAS  Google Scholar 

  75. Luther EM, Koehler Y, Diendorf J, Epple M, Dringen R (2011) Accumulation of silver nanoparticles by cultured primary brain astrocytes. Nanotechnology 22:375101

    Article  PubMed  CAS  Google Scholar 

  76. Geppert M, Hohnholt MC, Thiel K, Nurnberger S, Grunwald I, Rezwan K, Dringen R (2011) Uptake of dimercaptosuccinate-coated magnetic iron oxide nanoparticles by cultured brain astrocytes. Nanotechnology 22:145101

    Article  PubMed  CAS  Google Scholar 

  77. Lamkowsky MC, Geppert M, Schmidt MM, Dringen R (2012) Magnetic field-induced acceleration of the accumulation of magnetic iron oxide nanoparticles by cultured brain astrocytes. J Biomed Mater Res A 100:323–334

    Article  PubMed  CAS  Google Scholar 

  78. Hohnholt MC, Geppert M, Luther EM, Petters C, Bulcke F, Dringen R (2013) Handling of iron oxide and silver nanoparticles by astrocytes. Neurochem Res 38:227–239

    Article  PubMed  CAS  Google Scholar 

  79. Chen SH, Lin JK, Liu SH, Liang YC, Lin-Shiau SY (2008) Apoptosis of cultured astrocytes induced by the copper and neocuproine complex through oxidative stress and JNK activation. Toxicol Sci 102:138–149

    Article  PubMed  CAS  Google Scholar 

  80. Reddy PV, Rao KV, Norenberg MD (2008) The mitochondrial permeability transition, and oxidative and nitrosative stress in the mechanism of copper toxicity in cultured neurons and astrocytes. Lab Invest 88:816–830

    Article  PubMed  CAS  Google Scholar 

  81. Dringen R, Pawlowski PG, Hirrlinger J (2005) Peroxide detoxification by brain cells. J Neurosci Res 79:157–165

    Article  PubMed  CAS  Google Scholar 

  82. Hirrlinger J, Dringen R (2010) The cytosolic redox state of astrocytes: maintenance, regulation and functional implications for metabolite trafficking. Brain Res Rev 63:177–188

    Article  PubMed  CAS  Google Scholar 

  83. Jiang J, St Croix CM, Sussman N, Zhao Q, Pitt BR, Kagan VE (2002) Contribution of glutathione and metallothioneins to protection against copper toxicity and redox cycling: quantitative analysis using MT+/+ and MT−/− mouse lung fibroblast cells. Chem Res Toxicol 15:1080–1087

    Article  PubMed  CAS  Google Scholar 

  84. Petters C, Irrsack E, Koch M, Dringen R (2014) Uptake and metabolism of iron oxide nanoparticles in brain cells. Neurochem Res 39:1648–1660

    Article  PubMed  CAS  Google Scholar 

  85. Han X, Gelein R, Corson N, Wade-Mercer P, Jiang J, Biswas P, Finkelstein JN, Elder A, Oberdorster G (2011) Validation of an LDH assay for assessing nanoparticle toxicity. Toxicology 287:99–104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Krotkiewska B, Banas T (1992) Interaction of Zn2+ and Cu2+ ions with glyceraldehyde-3-phosphate dehydrogenase from bovine heart and rabbit muscle. Int J Biochem 24:1501–1505

    Article  PubMed  CAS  Google Scholar 

  87. Lai JC, Blass JP (1984) Neurotoxic effects of copper: inhibition of glycolysis and glycolytic enzymes. Neurochem Res 9:1699–1710

    Article  PubMed  CAS  Google Scholar 

  88. Takahashi S, Abe T, Gotoh J, Fukuuchi Y (2002) Substrate-dependence of reduction of MTT: a tetrazolium dye differs in cultured astroglia and neurons. Neurochem Int 40:441–448

    Article  PubMed  CAS  Google Scholar 

  89. Sheline CT, Choi EH, Kim-Han JS, Dugan LL, Choi DW (2002) Cofactors of mitochondrial enzymes attenuate copper-induced death in vitro and in vivo. Ann Neurol 52:195–204

    Article  PubMed  CAS  Google Scholar 

  90. Ferretti G, Bacchetti T, Moroni C, Vignini A, Curatola G (2003) Copper-induced oxidative damage on astrocytes: protective effect exerted by human high density lipoproteins. Biochim Biophys Acta 1635:48–54

    Article  PubMed  CAS  Google Scholar 

  91. Pickard MR, Jenkins SI, Koller CJ, Furness DN, Chari DM (2011) Magnetic nanoparticle labeling of astrocytes derived for neural transplantation. Tissue Eng Part C Methods 17:89–99

    Article  PubMed  CAS  Google Scholar 

  92. Rademacher T, Male DK (2014) Nanoparticle delivery compositions. US Patent US20140227186 A1

  93. Petters C, Thiel K, Dringen R (2015) Lysosomal iron libaration is responsible for the vulnerability of brain microglial cells to iron oxide nanoparticles: comparison with neurons and astrocytes. Nanotoxicology. doi:10.3109/17435390.2015.1071445

    PubMed  Google Scholar 

  94. Chiang HS, Maric M (2011) Lysosomal thiol reductase negatively regulates autophagy by altering glutathione synthesis and oxidation. Free Radic Biol Med 51:688–699

    Article  PubMed  CAS  Google Scholar 

  95. de Duve C (1983) Lysosomes revisited. Eur J Biochem 137:391–397

    Article  PubMed  Google Scholar 

  96. Wang Z, von dem Bussche A, Kabadi PK, Kane AB, Hurt RH (2013) Biological and environmental transformations of copper-based nanomaterials. ACS Nano 7:8715–8727

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Kim H, Wu X, Lee J (2013) SLC31 (CTR) family of copper transporters in health and disease. Mol Aspects Med 34:561–570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Pelizzoni I, Zacchetti D, Smith CP, Grohovaz F, Codazzi F (2012) Expression of divalent metal transporter 1 in primary hippocampal neurons: reconsidering its role in non-transferrin-bound iron influx. J Neurochem 120:269–278

    Article  PubMed  CAS  Google Scholar 

  99. Rae TD, Schmidt PJ, Pufahl RA, Culotta VC, O’Halloran TV (1999) Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. Science 284:805–808

    Article  PubMed  CAS  Google Scholar 

  100. Robinson NJ, Winge DR (2010) Copper metallochaperones. Annu Rev Biochem 79:537–562

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Dringen R, Hamprecht B (1998) Glutathione restoration as indicator for cellular metabolism of astroglial cells. Dev Neurosci 20:401–407

    Article  PubMed  CAS  Google Scholar 

  102. Aschner M, Conklin DR, Yao CP, Allen JW, Tan KH (1998) Induction of astrocyte metallothioneins (MTs) by zinc confers resistance against the acute cytotoxic effects of methylmercury on cell swelling, Na+ uptake, and K+ release. Brain Res 813:254–261

    Article  PubMed  CAS  Google Scholar 

  103. Aschner M, Lorscheider FL, Cowan KS, Conklin DR, Vimy MJ, Lash LH (1997) Metallothionein induction in fetal rat brain and neonatal primary astrocyte cultures by in utero exposure to elemental mercury vapor (Hg0). Brain Res 778:222–232

    Article  PubMed  CAS  Google Scholar 

  104. Lee SJ, Koh JY (2010) Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes. Mol Brain 3:30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Dineley KE, Scanlon JM, Kress GJ, Stout AK, Reynolds IJ (2000) Astrocytes are more resistant than neurons to the cytotoxic effects of increased [Zn(2+)]i. Neurobiol Dis 7:310–320

    Article  PubMed  CAS  Google Scholar 

  106. Luther EM, Schmidt MM, Diendorf J, Epple M, Dringen R (2012) Upregulation of metallothioneins after exposure of cultured primary astrocytes to silver nanoparticles. Neurochem Res 37:1639–1648

    Article  PubMed  CAS  Google Scholar 

  107. Speisky H, Gomez M, Burgos-Bravo F, Lopez-Alarcon C, Jullian C, Olea-Azar C, Aliaga ME (2009) Generation of superoxide radicals by copper-glutathione complexes: redox-consequences associated with their interaction with reduced glutathione. Bioorg Med Chem 17:1803–1810

    Article  PubMed  CAS  Google Scholar 

  108. Vasak M, Meloni G (2011) Chemistry and biology of mammalian metallothioneins. J Biol Inorg Chem 16:1067–1078

    Article  PubMed  CAS  Google Scholar 

  109. Telianidis J, Hung YH, Materia S, Fontaine SL (2013) Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis. Front Aging Neurosci 5:44

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. La Fontaine S, Mercer JF (2007) Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys 463:149–167

    Article  PubMed  CAS  Google Scholar 

  111. Kim BE, Petris MJ (2007) Phenotypic diversity of Menkes disease in mottled mice is associated with defects in localisation and trafficking of the ATP7A protein. J Med Genet 44:641–646

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Kaler SG (2011) ATP7A-related copper transport diseases-emerging concepts and future trends. Nat Rev Neurol 7:15–29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Tiffany-Castiglioni E, Hong S, Qian Y (2011) Copper handling by astrocytes: insights into neurodegenerative diseases. Int J Dev Neurosci 29:811–818

    Article  PubMed  CAS  Google Scholar 

  114. Choo XY, Alukaidey L, White AR, Grubman A (2013) Neuroinflammation and copper in Alzheimer’s disease. Int J Alzheimers Dis 2013:145345

    PubMed  PubMed Central  Google Scholar 

  115. Franklin CC, Backos DS, Mohar I, White CC, Forman HJ, Kavanagh TJ (2009) Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase. Mol Aspects Med 30:86–98

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Kranich O, Dringen R, Sandberg M, Hamprecht B (1998) Utilization of cysteine and cysteine precursors for the synthesis of glutathione in astroglial cultures: preference for cystine. Glia 22:11–18

    Article  PubMed  CAS  Google Scholar 

  117. Minich T, Riemer J, Schulz JB, Wielinga P, Wijnholds J, Dringen R (2006) The multidrug resistance protein 1 (Mrp1), but not Mrp5, mediates export of glutathione and glutathione disulfide from brain astrocytes. J Neurochem 97:373–384

    Article  PubMed  CAS  Google Scholar 

  118. Tadepalle N, Koehler Y, Brandmann M, Meyer N, Dringen R (2014) Arsenite stimulates glutathione export and glycolytic flux in viable primary rat brain astrocytes. Neurochem Int 76:1–11

    Article  PubMed  CAS  Google Scholar 

  119. Hirrlinger J, Schulz JB, Dringen R (2002) Glutathione release from cultured brain cells: multidrug resistance protein 1 mediates the release of GSH from rat astroglial cells. J Neurosci Res 69:318–326

    Article  PubMed  CAS  Google Scholar 

  120. Tulpule K, Schmidt MM, Boecker K, Goldbaum O, Richter-Landsberg C, Dringen R (2012) Formaldehyde induces rapid glutathione export from viable oligodendroglial OLN-93 cells. Neurochem Int 61:1302–1313

    Article  PubMed  CAS  Google Scholar 

  121. D’Ambrosi N, Rossi L (2015) Copper at synapse: release, binding and modulation of neurotransmission. Neurochem Int. doi:10.1016/j.neuint.2015.07.006

    PubMed  Google Scholar 

  122. Tiffany-Castiglion E, Qian Y (2001) Astroglia as metal depots: molecular mechanisms for metal accumulation, storage and release. Neurotoxicology 22:577–592

    Article  PubMed  CAS  Google Scholar 

  123. Dusek P, Roos PM, Litwin T, Schneider SA, Flaten TP, Aaseth J (2015) The neurotoxicity of iron, copper and manganese in Parkinson’s and Wilson’s diseases. J Trace Elem Med Biol 31:193–203

    Article  PubMed  CAS  Google Scholar 

  124. Scheiber IF, Dringen R, Mercer JFB (2013) Copper: effects of deficiency and overload. Met Ions Life Sci 13:359–387

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Biomolecular Interactions Bremen, Faculty 2 (Biology, Chemistry), University of Bremen, PO. Box 330440, 28334, Bremen, Germany

    Felix Bulcke & Ralf Dringen

  2. Center for Environmental Research and Sustainable Technology, Leobener Strasse, 28359, Bremen, Germany

    Felix Bulcke & Ralf Dringen

Authors
  1. Felix Bulcke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralf Dringen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ralf Dringen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Special Issue: 40th Year of Neurochemical Research.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bulcke, F., Dringen, R. Handling of Copper and Copper Oxide Nanoparticles by Astrocytes. Neurochem Res 41, 33–43 (2016). https://doi.org/10.1007/s11064-015-1688-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1688-9

Keywords

Search

Navigation