Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-26T09:29:12.948Z Has data issue: false hasContentIssue false
  • English
  • Français

Copper as a key regulator of cell signalling pathways

Published online by Cambridge University Press:  22 May 2014

Alexandra Grubman  and
Anthony R. White
Alexandra Grubman
Affiliation:
Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
Anthony R. White*
Affiliation:
Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
*
*Corresponding author: Anthony R. White, Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia. E-mail: arwhite@unimelb.edu.au
Get access Rights & Permissions [Opens in a new window]

Abstract

Copper is an essential element in many biological processes. The critical functions associated with copper have resulted from evolutionary harnessing of its potent redox activity. This same property also places copper in a unique role as a key modulator of cell signal transduction pathways. These pathways are the complex sequence of molecular interactions that drive all cellular mechanisms and are often associated with the interplay of key enzymes including kinases and phosphatases but also including intracellular changes in pools of smaller molecules. A growing body of evidence is beginning to delineate the how, when and where of copper-mediated control over cell signal transduction. This has been driven by research demonstrating critical changes to copper homeostasis in many disorders including cancer and neurodegeneration and therapeutic potential through control of disease-associated cell signalling changes by modulation of copper–protein interactions. This timely review brings together for the first time the diverse actions of copper as a key regulator of cell signalling pathways and discusses the potential strategies for controlling disease-associated signalling processes using copper modulators. It is hoped that this review will provide a valuable insight into copper as a key signal regulator and stimulate further research to promote our understanding of copper in disease and therapy.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 16 , 2014 , e11
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Maret, W. (2013) Zinc biochemistry: from a single zinc enzyme to a key element of life. Advances in Nutrition 4, 82-91CrossRefGoogle ScholarPubMed
2Ciuffreda, L. et al. (2013) Signaling intermediates (MAPK and PI3 K) as therapeutic targets in NSCLC. Current Pharmceutical Design PMID: 24138714Google Scholar
3Chen, G. and Goeddel, D.V. (2002) TNF-R1 signaling: a beautiful pathway. Science 296, 1634-1635CrossRefGoogle ScholarPubMed
4Ibanez, C.F. (2010) Beyond the cell surface: new mechanisms of receptor function. Biochemical and Biophysical Research Communications 396, 24-27CrossRefGoogle ScholarPubMed
5Latek, D. et al. (2012) G protein-coupled receptors – recent advances. Acta Biochimica Polonica 59, 515-529CrossRefGoogle ScholarPubMed
6Madhani, H.D. (2006) Functional analysis of protein kinase networks in living cells: beyond “knock-outs” and “knock-downs”. Methods 40, 251-254CrossRefGoogle ScholarPubMed
7Yan-Na, L., Ren-Zhong, W. and Zhao-Peng, L. (2013) Recent developments of small molecule PI3 K/mTOR dual inhibitors. Mini Reviews in Medicinal Chemistry 13, 2047-2059Google Scholar
8Kazi, J.U., Kabir, N.N. and Ronnstrand, L. (2013) Protein kinase C (PKC) as a drug target in chronic lymphocytic leukemia. Medical Oncology 30, 757Google Scholar
9Neuzillet, C. et al. (2013) MEK in cancer and cancer therapy. Pharmacology Therapy 141, 160-171Google Scholar
10Bubici, C. and Papa, S. (2013) JNK signaling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology 171, 24-37CrossRefGoogle Scholar
11Niederst, M.J. and Engelman, J.A. (2013) Bypass mechanisms of resistance to receptor tyrosine kinase inhibition in lung cancer. Science Signaling 6, re6CrossRefGoogle ScholarPubMed
12Chan, C.B. and Ye, K. (2013) Serine-arginine protein kinases: new players in neurodegenerative diseases? Reviews in Neuroscience 24, 401-413CrossRefGoogle ScholarPubMed
13Shukla, V., Skuntz, S. and Pant, H.C. (2012) Deregulated Cdk5 activity is involved in inducing Alzheimer's disease. Archives of Medical Research 43, 655-662Google Scholar
14Kanaan, N.M. et al. (2013) Axonal degeneration in Alzheimer's disease: when signaling abnormalities meet the axonal transport system. Experimental Neurology 246, 44-53CrossRefGoogle ScholarPubMed
15Wang, J.Z. et al. (2013) Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. Journal of Alzheimer's Disease 33(Suppl 1), S123-S139Google Scholar
16Wilhelmus, M.M. et al. (2012) Involvement and interplay of Parkin, PINK1, and DJ1 in neurodegenerative and neuroinflammatory disorders. Free Radical Biology and Medicine 53, 983-992CrossRefGoogle ScholarPubMed
17Bocharov, E.V. et al. (2013) Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies. Structure 21, 2087-2093CrossRefGoogle ScholarPubMed
18Shi, J. and Wei, L. (2013) Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil. Journal of Cardiovascular Pharmacology 62, 341-354Google Scholar
19Provenzano, A., Kurian, S. and Abraham, J. (2013) Overcoming endocrine resistance in breast cancer: role of the PI3 K and the mTOR pathways. Expert Reviews in Anticancer Therapeutics 13, 143-147CrossRefGoogle Scholar
20Banci, L. et al. (2010) Cellular copper distribution: a mechanistic systems biology approach. Cellular and Molecular Life Sciences 67, 2563-2589Google Scholar
21Telianidis, J. et al. (2013) Role of the P-type ATPases, ATP7A and ATP7B in brain copper homeostasis. Frontiers in Aging Neuroscience 5, 44CrossRefGoogle ScholarPubMed
22Nevitt, T., Ohrvik, H. and Thiele, D.J. (2012) Charting the travels of copper in eukaryotes from yeast to mammals. Biochimica Biophysica Acta 1823, 1580-1593CrossRefGoogle ScholarPubMed
23McMillin, G.A., Travis, J.J. and Hunt, J.W. (2009) Direct measurement of free copper in serum or plasma ultrafiltrate. American Journal of Clinical Pathology 131, 160-165Google Scholar
24Kodama, H. et al. (1988) Does CSF copper level in Wilson disease reflect copper accumulation in the brain? Pediatric Neurology 4, 35-37Google Scholar
25Gaier, E.D., Eipper, B.A. and Mains, R.E. (2013) Copper signaling in the mammalian nervous system: synaptic effects. Journal of Neuroscience Research 91, 2-19CrossRefGoogle ScholarPubMed
26Kim, H., Wu, X. and Lee, J. (2013) SLC31 (CTR) family of copper transporters in health and disease. Molecular Aspects of Medicine 34, 561-570CrossRefGoogle ScholarPubMed
27Hasan, N.M. and Lutsenko, S. (2012) Regulation of copper transporters in human cells. Current Topics in Membranes 69, 137-161Google Scholar
28Wee, N.K. et al. (2013) The mammalian copper transporters CTR1 and CTR2 and their roles in development and disease. International Journal of Biochemistry and Cell Biology 45, 960-963CrossRefGoogle ScholarPubMed
29Squitti, R. and Polimanti, R. (2013) Copper phenotype in Alzheimer's disease: dissecting the pathway. American Journal of Neurodegenerative Disease 2, 46-56Google ScholarPubMed
30Greenough, M.A., Camakaris, J. and Bush, A.I. (2013) Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Neurochemistry International 62, 540-555Google Scholar
31Tisato, F. et al. (2010) Copper in diseases and treatments, and copper-based anticancer strategies. Medical Research Reviews 30, 708-749Google Scholar
32Bourassa, M.W. and Miller, L.M. (2012) Metal imaging in neurodegenerative diseases. Metallomics 4, 721-738Google Scholar
33New, E.J. (2012) Tools to study distinct metal pools in biology. Dalton Transactions 42, 3210–329CrossRefGoogle ScholarPubMed
34Miller, E.W. et al. (2006) Preparation and use of Coppersensor-1, a synthetic fluorophore for live-cell copper imaging. Nature Protocols 1, 824-827CrossRefGoogle ScholarPubMed
35Domaille, D.W., Que, E.L. and Chang, C.J. (2008) Synthetic fluorescent sensors for studying the cell biology of metals. Nature Chemical Biology 4, 168-175Google Scholar
36Dodani, S.C. et al. (2011) A targetable fluorescent sensor reveals that copper-deficient SCO1 and SCO2 patient cells prioritize mitochondrial copper homeostasis. Journal of the American Chemical Society 133, 8606-8616Google Scholar
37Price, K.A. et al. (2012) The challenges of using a copper fluorescent sensor (CS1) to track intracellular distributions of copper in neuronal and glial cells. Chemical Science 3, 2748-2759Google Scholar
38Travaglia, A. et al. (2012) Copper, BDNF and its N-terminal domain: inorganic features and biological perspectives. Chemistry 18, 15618-15631CrossRefGoogle ScholarPubMed
39Travaglia, A. et al. (2011) The inorganic perspective of nerve growth factor: interactions of Cu2+ and Zn2+ with the N-terminus fragment of nerve growth factor encompassing the recognition domain of the TrkA receptor. Chemistry 17, 3726-3738CrossRefGoogle ScholarPubMed
40Ross, G.M. et al. (2001) The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis. Journal of Neurochemistry 78, 515-523Google Scholar
41Wang, W. et al. (1999) Zinc and copper inhibit nerve growth factor-mediated protection from oxidative stress-induced apoptosis. Neuroscience Letters 259, 115-118Google Scholar
42Birkaya, B. and Aletta, J.M. (2005) NGF promotes copper accumulation required for optimum neurite outgrowth and protein methylation. Journal of Neurobiology 63, 49-61CrossRefGoogle ScholarPubMed
43Di Serio, C. et al. (2008) The release of fibroblast growth factor-1 from melanoma cells requires copper ions and is mediated by phosphatidylinositol 3-kinase/Akt intracellular signaling pathway. Cancer Letters 267, 67-74CrossRefGoogle ScholarPubMed
44Soldi, R. et al. (2007) Sphingosine kinase 1 is a critical component of the copper-dependent FGF1 export pathway. Experimental Cell Research 313, 3308-3318CrossRefGoogle ScholarPubMed
45Samet, J.M. et al. (1998) Activation of MAPKs in human bronchial epithelial cells exposed to metals. American Journal of Physiology 275, L551-L558Google Scholar
46Samet, J.M. et al. (1999) Tyrosine phosphatases as targets in metal-induced signaling in human airway epithelial cells. American Journal of Respiratory Cell and Molecular Biology 21, 357-364Google Scholar
47Wu, W. et al. (1999) Activation of the EGF receptor signaling pathway in human airway epithelial cells exposed to metals. American Journal of Physiology 277, L924-L931Google ScholarPubMed
48Price, K.A. et al. (2009) Sustained activation of glial cell epidermal growth factor receptor by bis(thiosemicarbazonato) metal complexes is associated with inhibition of protein tyrosine phosphatase activity. Journal of Medicinal Chemistry 52, 6606-6620CrossRefGoogle ScholarPubMed
49Crouch, P.J. et al. (2009) Increasing Cu bioavailability inhibits Abeta oligomers and tau phosphorylation. Proceedings of the National Academy of Sciences of the United States of America 106, 381-386CrossRefGoogle ScholarPubMed
50Hehlgans, S., Haase, M. and Cordes, N. (2007) Signalling via integrins: implications for cell survival and anticancer strategies. Biochimica Biophysica Acta 1775, 163-180Google ScholarPubMed
51Fan, C. et al. (2010) A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin beta4 in H322 lung carcinoma cells. European Journal of Medicinal Chemistry 45, 1438-1446Google Scholar
52Fan, C. et al. (2009) Novel complex of copper and a salicylaldehyde pyrazole hydrazone derivative induces apoptosis through up-regulating integrin beta 4 in vascular endothelial cells. Chemical Research and Toxicology 22, 1517-1525CrossRefGoogle Scholar
53Tenaud, I. et al. (1999) In vitro modulation of keratinocyte wound healing integrins by zinc, copper and manganese. British Journal of Dermatology 140, 26-34Google Scholar
54Tenaud, I. et al. (2000) Zinc, copper and manganese enhanced keratinocyte migration through a functional modulation of keratinocyte integrins. Experimental Dermatology 9, 407-416Google Scholar
55Kang, Y.A. et al. (2009) Copper-GHK increases integrin expression and p63 positivity by keratinocytes. Archives of Dermatological Research 301, 301-306Google Scholar
56Weaver, M.S., Workman, G. and Sage, E.H. (2008) The copper binding domain of SPARC mediates cell survival in vitro via interaction with integrin beta1 and activation of integrin-linked kinase. Journal of Biological Chemistry 283, 22826-22837CrossRefGoogle ScholarPubMed
57Zhou, Y., Bourcy, K. and Kang, Y.J. (2009) Copper-induced regression of cardiomyocyte hypertrophy is associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway. Cardiovascular Research 84, 54-63CrossRefGoogle ScholarPubMed
58Mizuno, S. et al. (2012) Copper deficiency induced emphysema is associated with focal adhesion kinase inactivation. PLoS One 7, e30678Google Scholar
59Price, K.A. et al. (2008) Activation of epidermal growth factor receptor by metal–ligand complexes decreases levels of extracellular amyloid beta peptide. International Journal of Biochemistry and Cell Biology 40, 1901-1917CrossRefGoogle ScholarPubMed
60Hornshaw, M.P. et al. (1995) Copper binding to the N-terminal tandem repeat region of mammalian and avian prion protein: structural studies using synthetic peptides. Biochemical and Biophysical Research Communications 214, 993-999Google Scholar
61Brown, D.R. et al. (1997) The cellular prion protein binds copper in vivo. Nature 390, 684-687CrossRefGoogle ScholarPubMed
62Stevens, D.J. et al. (2009) Early onset prion disease from octarepeat expansion correlates with copper binding properties. PLoS Pathogens 5, e1000390CrossRefGoogle ScholarPubMed
63Sigurdsson, E.M. et al. (2003) Copper chelation delays the onset of prion disease. Journal of Biological Chemistry 278, 46199-46202CrossRefGoogle ScholarPubMed
64Siggs, O.M. et al. (2012) Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease. Proceedings of the National Academy of Sciences of the United States of America 109, 13733-13738Google Scholar
65Mitteregger, G. et al. (2009) Role of copper and manganese in prion disease progression. Brain Research 1292, 155-164Google Scholar
66Varela-Nallar, L., Gonzalez, A. and Inestrosa, N.C. (2006) Role of copper in prion diseases: deleterious or beneficial? Current Pharmaceutical Design 12, 2587-2595CrossRefGoogle ScholarPubMed
67Armendariz, A.D. et al. (2004) Gene expression profiling in chronic copper overload reveals upregulation of Prnp and App. Physiological Genomics 20, 45-54Google Scholar
68Bellingham, S.A. et al. (2009) Regulation of prion gene expression by transcription factors SP1 and metal transcription factor-1. Journal of Biological Chemistry 284, 1291-1301Google Scholar
69Varela-Nallar, L. et al. (2006) Induction of cellular prion protein gene expression by copper in neurons. American Journal of Physiology, Cell Physiology 290, C271-C281CrossRefGoogle ScholarPubMed
70Marchetti, C., Baranowska-Bosiacka, I. and Gavazzo, P. (2013) Multiple effects of copper on NMDA receptor currents. Brain Research 1542, 20-31Google Scholar
71Schlief, M.L. et al. (2006) Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity. Proceedings of the National Academy of Sciences of the United States of America 103, 14919-14924Google Scholar
72Acuna-Castillo, C. et al. (2007) Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X7 purinergic receptor. Journal of Neurochemistry 101, 17-26Google Scholar
73Huidobro-Toro, J.P., Lorca, R.A. and Coddou, C. (2008) Trace metals in the brain: allosteric modulators of ligand-gated receptor channels, the case of ATP-gated P2X receptors. European Biophysics Journal 37, 301-314Google Scholar
74Punthambaker, S. and Hume, R.I. (2013) Potent and long-lasting inhibition of human P2X2 receptors by copper. Neuropharmacology 77C, 167-176Google Scholar
75Tamano, H. and Takeda, A. (2011) Dynamic action of neurometals at the synapse. Metallomics 3, 656-661Google Scholar
76Ostrakhovitch, E.A. et al. (2002) Copper ions strongly activate the phosphoinositide-3-kinase/Akt pathway independent of the generation of reactive oxygen species. Archives of Biochemistry and Biophysics 397, 232-239Google Scholar
77Eckers, A., Reimann, K. and Klotz, L.O. (2009) Nickel and copper ion-induced stress signaling in human hepatoma cells: analysis of phosphoinositide 3′-kinase/Akt signaling. Biometals 22, 307-316CrossRefGoogle ScholarPubMed
78Ostrakhovitch, E.A. and Cherian, M.G. (2004) Differential regulation of signal transduction pathways in wild type and mutated p53 breast cancer epithelial cells by copper and zinc. Archives of Biochemistry and Biophysics 423, 351-361Google Scholar
79Barthel, A. et al. (2007) Stimulation of phosphoinositide 3-kinase/Akt signaling by copper and zinc ions: mechanisms and consequences. Archives of Biochemistry and Biophysics 463, 175-182Google Scholar
80Tsai, C.Y. et al. (2012) Copper influx transporter 1 is required for FGF, PDGF and EGF-induced MAPK signaling. Biochemical Pharmacology 84, 1007-1013Google Scholar
81Turski, M.L. et al. (2012) A novel role for copper in Ras/mitogen-activated protein kinase signaling. Molecular and Cellular Biology 32, 1284-1295CrossRefGoogle ScholarPubMed
82Nawaz, M. et al. (2006) Copper-induced stimulation of extracellular signal-regulated kinase in trout hepatocytes: the role of reactive oxygen species, Ca2 +, and cell energetics and the impact of extracellular signal-regulated kinase signaling on apoptosis and necrosis. Toxicological Sciences 92, 464-475CrossRefGoogle ScholarPubMed
83Piret, J.P. et al. (2012) Copper(II) oxide nanoparticles penetrate into HepG2 cells, exert cytotoxicity via oxidative stress and induce pro-inflammatory response. Nanoscale 4, 7168-7184CrossRefGoogle ScholarPubMed
84Chen, S.H. et al. (2008) Involvement of activating transcription factors JNK, NF-kappaB, and AP-1 in apoptosis induced by pyrrolidine dithiocarbamate/Cu complex. European Journal of Pharmacology 594, 9-17Google Scholar
85Wu, C.C. et al. (2012) Involvement of oxidative stress-induced ERK/JNK activation in the Cu(2+)/pyrrolidine dithiocarbamate complex-triggered mitochondria-regulated apoptosis in pancreatic beta-cells. Toxicology Letters 208, 275-285CrossRefGoogle ScholarPubMed
86Chen, Y.W. et al. (2010) Pyrrolidine dithiocarbamate (PDTC)/Cu complex induces lung epithelial cell apoptosis through mitochondria and ER-stress pathways. Toxicology Letters 199, 333-340Google Scholar
87Liu, P. et al. (2012) Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. British Journal of Cancer 107, 1488-1497CrossRefGoogle ScholarPubMed
88Xu, B. et al. (2011) Disulfiram/copper complex activated JNK/c-jun pathway and sensitized cytotoxicity of doxorubicin in doxorubicin resistant leukemia HL60 cells. Blood Cells, Molecules and Diseases 47, 264-269Google Scholar
89Chen, S.H. et al. (2008) Apoptosis of cultured astrocytes induced by the copper and neocuproine complex through oxidative stress and JNK activation. Toxicological Science 102, 138-149Google Scholar
90Mattie, M.D., McElwee, M.K. and Freedman, J.H. (2008) Mechanism of copper-activated transcription: activation of AP-1, and the JNK/SAPK and p38 signal transduction pathways. Journal of Molecular Biology 383, 1008-1018CrossRefGoogle ScholarPubMed
91Moon, S.K. et al. (2004) PDTC, metal chelating compound, induces G1 phase cell cycle arrest in vascular smooth muscle cells through inducing p21Cip1 expression: involvement of p38 mitogen activated protein kinase. Journal of Cellular Physiology 198, 310-323Google Scholar
92Chen, X. et al. (2009) p38 and ERK, but not JNK, are involved in copper-induced apoptosis in cultured cerebellar granule neurons. Biochemical and Biophysical Research Communications 379, 944-948Google Scholar
93Kadowaki, S. et al. (2009) Trientine, a copper-chelating agent, induced apoptosis in murine fibrosarcoma cells by activation of the p38 MAPK pathway. Journal of Veterinary Medical Science 71, 1541-1544Google Scholar
94Wang, Q. et al. (2010) Potent inhibition of protein tyrosine phosphatase 1B by copper complexes: implications for copper toxicity in biological systems. Chemical Communications (Cambridge) 46, 3547-3549Google Scholar
95Yuan, C. et al. (2012) Potent and selective inhibition of T-cell protein tyrosine phosphatase (TCPTP) by a dinuclear copper(II) complex. Chemical Communications (Cambridge) 48, 1153-1155CrossRefGoogle ScholarPubMed
96Bica, L. et al. (2014) Neuroprotective copper bis(thiosemicarbazonato) complexes promote neurite elongation. PLoS One 9, e90070Google Scholar
97Urquiza, N.M. et al. (2010) Copper(II) complexes of methimazole, an anti Grave's disease drug. Synthesis, characterization and its potential biological behavior as alkaline phosphatase inhibitor. Biometals 23, 255-264CrossRefGoogle ScholarPubMed
98Hanahisa, Y. and Yamaguchi, M. (1998) Inhibitory effect of zinc and copper on phosphatase activity in the brain cytosol of rats: involvement of SH groups. Biological and Pharmaceutical Bulletin 21, 1222-1225CrossRefGoogle ScholarPubMed
99Zhang, D. and Glass, C. (2013) Towards an understanding of cell-specific functions of signal-dependent transcription factors. Journal of Molecular Endocrinology 51, T37-50CrossRefGoogle ScholarPubMed
100Rutherford, J.C. and Bird, A.J. (2004) Metal-responsive transcription factors that regulate iron, zinc, and copper homeostasis in eukaryotic cells. Eukaryotic Cell 3, 1-13Google Scholar
101Radtke, F. et al. (1995) Functional domains of the heavy metal-responsive transcription regulator MTF-1. Nucleic Acids Research 23, 2277-2286Google Scholar
102Song, M.O. et al. (2014) The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription. Experimental Cell Research 322, 39-50CrossRefGoogle ScholarPubMed
103Wang, X.J. et al. (2010) Activation of the NRF2 signaling pathway by copper-mediated redox cycling of para- and ortho-hydroquinones. Chemical Biology 17, 75-85CrossRefGoogle ScholarPubMed
104Song, I.S. et al. (2008) Transcription factor Sp1 plays an important role in the regulation of copper homeostasis in mammalian cells. Molecular Pharmacology 74, 705-713CrossRefGoogle ScholarPubMed
105Cherian, M.G. and Apostolova, M.D. (2000) Nuclear localization of metallothionein during cell proliferation and differentiation. Cellular and Molecular Biology (Noisy-le-grand) 46, 347-356Google Scholar
106Itoh, S. et al. (2008) Novel role of antioxidant-1 (Atox1) as a copper-dependent transcription factor involved in cell proliferation. Journal of Biological Chemistry 283, 9157-9167Google Scholar
107Muller, P.A. and Klomp, L.W. (2009) ATOX1: a novel copper-responsive transcription factor in mammals? International Journal of Biochemistry and Cell Biology 41, 1233-1236CrossRefGoogle ScholarPubMed
108McElwee, M.K., Song, M.O. and Freedman, J.H. (2009) Copper activation of NF-kappaB signaling in HepG2 cells. Journal of Molecular Biology 393, 1013-1021Google Scholar
109Song, M.O., Li, J. and Freedman, J.H. (2009) Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiological Genomics 38, 386-401Google Scholar
110Satake, H. et al. (1995) Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha. Biochemical and Biophysical Research Communications 216, 568-573Google Scholar
111Walter, P.L. et al. (2006) Modulation of FoxO signaling in human hepatoma cells by exposure to copper or zinc ions. Archives of Biochemistry and Biophysics 454, 107-113Google Scholar
112Hoti, N. et al. (2004) p53-dependent apoptotic mechanism of a new designer bimetallic compound tri-phenyl tin benzimidazolethiol copper chloride (TPT-CuCl2): in vivo studies in Wistar rats as well as in vitro studies in human cervical cancer cells. Journal of Pharmacology and Experimental Therapeutics 311, 22-33Google Scholar
113Bartuzi, P., Hofker, M.H. and van de Sluis, B. (2013) Tuning NF-kappaB activity: a touch of COMMD proteins. Biochimica et Biophysica Acta 1832, 2315-2321Google Scholar
114Sarkar, B. and Roberts, E.A. (2011) The puzzle posed by COMMD1, a newly discovered protein binding Cu(II). Metallomics 3, 20-27Google Scholar
115Trempe, J.F. and Fon, E.A. (2013) Structure and function of Parkin, PINK1, and DJ-1, the three musketeers of neuroprotection. Frontiers in Neurology 4, 38Google Scholar
116Clayton, E.L., Minogue, S. and Waugh, M.G. (2013) Phosphatidylinositol 4-kinases and PI4P metabolism in the nervous system: roles in psychiatric and neurological diseases. Molecular Neurobiology 47, 361-372Google Scholar
117Um, J.W. and Strittmatter, S.M. (2013) Amyloid-beta induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease. Prion 7, 37-41Google Scholar
118Russo, E. et al. (2012) The mTOR signaling pathway in the brain: focus on epilepsy and epileptogenesis. Molecular Neurobiology 46, 662-681Google Scholar
119Jellinger, K.A. (2013) The relevance of metals in the pathophysiology of neurodegeneration, pathological considerations. International Reviews of Neurobiology 110C, 1-47Google Scholar
120Malm, T.M. et al. (2007) Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting beta-amyloid burden. Journal of Neuroscience 27, 3712-3721CrossRefGoogle ScholarPubMed
121Kitazawa, M., Cheng, D. and Laferla, F.M. (2009) Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. Journal of Neurochemistry 108, 1550-1560CrossRefGoogle Scholar
122Persichini, T. et al. (2006) Copper activates the NF-kappaB pathway in vivo. Antioxidants and Redox Signaling 8, 1897-1904Google Scholar
123Davis, C.D. and Johnson, W.T. (2001) Dietary copper and dimethylhydrazine affect protein kinase C isozyme protein and mRNA expression and the formation of aberrant crypts in colon of rats. Biofactors 15, 11-26Google Scholar
124Leung, M.H., Harada, T. and Kee, T.W. (2013) Delivery of curcumin and medicinal effects of the copper(II)–curcumin complexes. Current Pharmaceutical Design 19, 2070-2083Google ScholarPubMed
125Pan, J. et al. (2012) Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson's disease through suppressing mitochondria dysfunction. Translational Neurodegeneration 1, 16Google Scholar
126Jiang, H. et al. (2011) Activation of nuclear factor erythroid 2-related factor 2 cytoprotective signaling by curcumin protect primary spinal cord astrocytes against oxidative toxicity. Biological and Pharmaceutical Bulletin 34, 1194-1197CrossRefGoogle ScholarPubMed
127Liu, Z. et al. (2011) Curcumin protects against A53 T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacology Research 63, 439-444Google Scholar
128Wang, M.S. et al. (2010) Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model. BMC Neuroscience 11, 57Google Scholar
129Grubman, A., White, A.R. and Liddell, J.R. (2013) Mitochondrial metals as a potential therapeutic target in neurodegeneration. British Journal of Pharmacology 171, 2159-2173CrossRefGoogle Scholar
130Iwunze, M.O. and McEwan, D. (2004) Peroxynitrite interaction with curcumin solubilized in ethanolic solution. Cellular and Molecular Biology (Noisy-le-grand) 50, 749-752Google Scholar
131Dairam, A. et al. (2008) Antioxidant and iron-binding properties of curcumin, capsaicin, and S-allylcysteine reduce oxidative stress in rat brain homogenate. Journal of Agriculture and Food Chemistry 56, 3350-3356Google Scholar
132Garcia, C.R. et al. (2012) Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism. Dalton Transactions 41, 6458-6467Google Scholar
133Ferrari, E. et al. (2013) Metal binding ability of curcumin derivatives: a theoretical vs. experimental approach. Dalton Transactions 42, 5304-5313Google Scholar
134Lou, J.R. et al. (2010) Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways. Anticancer Research 30, 3249-3255Google ScholarPubMed
135Kunwar, A. et al. (2007) Delayed activation of PKCdelta and NFkappaB and higher radioprotection in splenic lymphocytes by copper (II)-Curcumin (1:1) complex as compared to curcumin. Journal of Cellular Biochemistry 102, 1214-1224Google Scholar
136John, V.D., Kuttan, G. and Krishnankutty, K. (2002) Anti-tumour studies of metal chelates of synthetic curcuminoids. Journal of Experimental and Clinical Cancer Research 21, 219-224Google Scholar
137Pan, Q., Bao, L.W. and Merajver, S.D. (2003) Tetrathiomolybdate inhibits angiogenesis and metastasis through suppression of the NFkappaB signaling cascade. Molecular Cancer Research 1, 701-706Google Scholar
138White, A.R. et al. (2006) Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent up-regulation of metalloprotease activity. Journal of Biological Chemistry 281, 17670-17680Google Scholar
139Daniel, K.G. et al. (2005) Clioquinol and pyrrolidine dithiocarbamate complex with copper to form proteasome inhibitors and apoptosis inducers in human breast cancer cells. Breast Cancer Research 7, R897-R908Google Scholar
140Ding, W.Q. et al. (2005) Anticancer activity of the antibiotic clioquinol. Cancer Research 65, 3389-3395Google Scholar
141Daniel, K.G. et al. (2007) Copper-binding compounds as proteasome inhibitors and apoptosis inducers in human cancer. Frontiers in Bioscience 12, 135-144CrossRefGoogle ScholarPubMed
142Chen, H.L. et al. (2009) Synthesis and pharmacological exploitation of clioquinol-derived copper-binding apoptosis inducers triggering reactive oxygen species generation and MAPK pathway activation. Bioorganic and Medicinal Chemistry 17, 7239-7247Google Scholar
143Laine, A.L. and Passirani, C. (2012) Novel metal-based anticancer drugs: a new challenge in drug delivery. Current Opinions in Pharmacology 12, 420-426Google Scholar
144Duncan, C. and White, A.R. (2012) Copper complexes as therapeutic agents. Metallomics 4, 127-138Google Scholar
145Colotti, G. et al. (2012) Metals and metal derivatives in medicine. Mini Reviews in Medicinal Chemistry PMID: 22512556Google Scholar
146Filomeni, G. et al. (2009) The isatin-Schiff base copper(II) complex Cu(isaepy)2 acts as delocalized lipophilic cation, yields widespread mitochondrial oxidative damage and induces AMP-activated protein kinase-dependent apoptosis. Carcinogenesis 30, 1115-1124Google Scholar
147Shrivastav, A. et al. (2006) Copper(II) and manganese(III) complexes of N'-[(2-hydroxy phenyl) carbonothioyl] pyridine-2-carbohydrazide: novel therapeutic agents for cancer. Biochimie 88, 1209-1216Google Scholar
148Trejo-Solis, C. et al. (2012) Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and JNK activation. BMC Cancer 12, 156Google Scholar
149Lutsenko, S. (2010) Human copper homeostasis: a network of interconnected pathways. Current Opinions in Chemical Biology 14, 211-217Google Scholar
150Choo, X.Y. et al. (2013) Neuroinflammation and copper in Alzheimer's disease. International Journal of Alzheimer's Disease 2013, 145345CrossRefGoogle ScholarPubMed
151Gupte, A. and Mumper, R.J. (2009) Elevated copper and oxidative stress in cancer cells as a target for cancer treatment. Cancer Treatment Reviews 35, 32-46Google Scholar
152Rupesh, K.R. et al. (2010) 2,2′-Bipyridyl based copper complexes down regulate expression of pro-inflammatory cytokines and suppress MAPKs in mitogen induced peripheral blood mononuclear cells. European Journal of Medicinal Chemistry 45, 2141-2146Google Scholar
153Rushworth, G.F. and Megson, I.L. (2014) Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacology and Therapeutics 141, 150-159Google Scholar
154Aruoma, O.I. et al. (1989) The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radical Biology and Medicine 6, 593-597Google Scholar
155Zheng, J. et al. (2010) N-Acetylcysteine interacts with copper to generate hydrogen peroxide and selectively induce cancer cell death. Cancer Letters 298, 186-194Google Scholar
156Offen, D. et al. (2004) A low molecular weight copper chelator crosses the blood–brain barrier and attenuates experimental autoimmune encephalomyelitis. Journal of Neurochemistry 89, 1241-1251Google Scholar
157Taba, P. (2013) Metals and movement disorders. Current Opinions in Neurology 26, 435-441Google Scholar
158Parker, S.J. et al. (2013) Biometals in rare neurodegenerative disorders of childhood. Frontiers in Aging Neuroscience 5, 14Google Scholar
159Ayton, S., Lei, P. and Bush, A.I. (2013) Metallostasis in Alzheimer's disease. Free Radical Biology and Medicine 62, 76-89Google Scholar
160Ward, R.J., Dexter, D.T. and Crichton, R.R. (2012) Chelating agents for neurodegenerative diseases. Current Medicinal Chemistry 19, 2760-2772Google Scholar
161Schrag, M. 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. Progress in Neurobiology 94, 296-306Google Scholar
162Bica, L. et al. (2009) Metallo-complex activation of neuroprotective signalling pathways as a therapeutic treatment for Alzheimer's disease. Molecular Biosystems 5, 134-142Google Scholar
163Barnham, K.J. et al. (2004) Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease beta-amyloid. FASEB Journal 18, 1427-1429Google Scholar
164Adlard, P.A. et al. (2010) Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic and memory deficits of Alzheimer's disease? Journal of Neuroscience 30, 1631-1636Google Scholar
165Atwood, C.S. et al. (1998) Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis. Journal of Biological Chemistry 273, 12817-12826Google Scholar
166Curtain, C.C. et al. (2001) Alzheimer's disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits. Journal of Biological Chemistry 276, 20466-20473CrossRefGoogle ScholarPubMed
167Huang, X. et al. (2004) Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptides. Journal of Biological Inorganic Chemistry 9, 954-960Google Scholar
168Multhaup, G. et al. (1996) The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I). Science 271, 1406-1409Google Scholar
169White, A.R. et al. (1999) The Alzheimer's disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures. Journal of Neuroscience 19, 9170-9179Google Scholar
170Acevedo, K.M. et al. (2014) Phosphorylation of amyloid precursor protein at Threonine-668 is essential for its copper-responsive trafficking in SH-SY5Y neuroblastoma cells. Journal of Biological Chemistry 289, 11007-11019Google Scholar
171Cherny, R.A. et al. (2001) Treatment with a copper–zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30, 665-676Google Scholar
172Ritchie, C.W. et al. (2003) Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Archives of Neurology 60, 1685-1691Google Scholar
173Filiz, G. et al. (2008) Clioquinol inhibits peroxide-mediated toxicity through up-regulation of phosphoinositol-3-kinase and inhibition of p53 activity. International Journal of Biochemistry and Cell Biology 40, 1030-1042Google Scholar
174Caragounis, A. et al. (2007) Differential modulation of Alzheimer's disease amyloid beta-peptide accumulation by diverse classes of metal ligands. Biochemical Journal 407, 435-450Google Scholar
175Crouch, P.J. et al. (2011) The Alzheimer's therapeutic PBT2 promotes amyloid-beta degradation and GSK3 phosphorylation via a metal chaperone activity. Journal of Neurochemistry 119, 220-230Google Scholar
176Parker, S.J. et al. (2012) Inhibition of TDP-43 Accumulation by Bis(thiosemicarbazonato)-Copper Complexes. PLoS One 7, e42277Google Scholar
177Soon, C.P. et al. (2011) Diacetylbis(N(4)-methylthiosemicarbazonato) copper(II) (CuII(atsm)) protects against peroxynitrite-induced nitrosative damage and prolongs survival in amyotrophic lateral sclerosis mouse model. Journal of Biological Chemistry 286, 44035-44044Google Scholar
178Hung, L.W. et al. (2012) The hypoxia imaging agent Cu-II(atsm) is neuroprotective and improves motor and cognitive functions in multiple animal models of Parkinson's disease. Journal of Experimental Medicine 209, 837-854Google Scholar
179Akatsu, H. et al. (2012) Transition metal abnormalities in progressive dementias. Biometals 25, 337-350Google Scholar
180Crouch, P.J. and Barnham, K.J. (2012) Therapeutic redistribution of metal ions to treat Alzheimer's disease. Accounts of Chemical Research 45, 1604-1611Google Scholar
181Donnelly, P.S. et al. (2008) Selective intracellular release of copper and zinc ions from bis(thiosemicarbazonato) complexes reduces levels of Alzheimer disease amyloid-beta peptide. Journal of Biological Chemistry 283, 4568-4577Google Scholar
182McAllum, E.J. et al. (2013) Therapeutic effects of Cu(atsm) in the SOD1-G37R mouse model of amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 14, 586-590Google Scholar