Clioquinol induces autophagy in cultured astrocytes and neurons by acting as a zinc ionophore

Neurobiology of Disease

Volumn 42, Issue 3, 2011, Pages 242-251

  Park, Mi Ha ^a,b   Lee, Sook Jeong ^b   Byun, Hyae ran ^b   Kim, Yunha ^b   Oh, Young J ^a   Koh, Jae Young ^b,c   Hwang, Jung Jin ^b  

^a Yonsei University   (South Korea)

^b University of Ulsan College of Medicine   (South Korea)

^c University of Ulsan   (South Korea)

Author keywords

Alzheimer's disease; Amyloid; Autolysosome; Autophagosome; Huntington's disease; Neuronal death

Indexed keywords

3 METHYLADENINE; AMYLOID BETA PROTEIN; BECLIN 1; CLIOQUINOL; GREEN FLUORESCENT PROTEIN; HUNTINGTIN; IONOPHORE; MICROTUBULE ASSOCIATED PROTEIN; N,N,N',N' TETRAKIS(2 PYRIDYLMETHYL)ETHYLENEDIAMINE; PYRITHIONE ZINC; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ZINC; ZINC IONOPHORE;

ANIMAL CELL; ARTICLE; ASTROCYTE; AUTOPHAGY; CELL VACUOLE; CHELATION; CONTROLLED STUDY; CYTOSOL; FETUS; FLUORESCENCE MICROSCOPY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; ION TRANSPORT; MOUSE; NERVE CELL; NERVE CELL CULTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN EXPRESSION; SENILE PLAQUE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; ASTROCYTES; AUTOPHAGY; BLOTTING, WESTERN; CELL LINE, TUMOR; CLIOQUINOL; IMMUNOHISTOCHEMISTRY; IONOPHORES; MICE; MICROFILAMENT PROTEINS; MICROSCOPY, CONFOCAL; NEURONS; ZINC;

EID: 79954628520     PISSN: 09699961     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.nbd.2011.01.009     Document Type: Article

References (36)

1. Adlard P.A., Bush A.I. Metals and Alzheimer's disease. J. Alzheimers Dis. 2006, 10:145-163.
2. Adlard P.A., et al. Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron 2008, 59:43-55.
3. Bush A.I., Pettingell W.H., Multhaup G., d Paradis M., Vonsattel J.P., Gusella J.F., Beyreuther K., Masters C.L., Tanzi R.E. Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 1994, 265:1464-1467.
4. Canzoniero L.M., Manzerra P., Sheline C.T., Choi D.W. Membrane-permeant chelators can attenuate Zn2+ -induced cortical neuronal death. Neuropharmacology 2003, 45:420-428.
5. Cherny R.A., Atwood C.S., Xilinas M.E., Gray D.N., Jones W.D., McLean C.A., Barnham K.J., Volitakis I., Fraser F.W., Kim Y., Huang X., Goldstein L.E., Moir R.D., Lim J.T., Beyreuther K., Zheng H., Tanzi R.E., Masters C.L., Bush A.I. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 2001, 30:665-676.
6. Choi D.W. Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci. Lett. 1985, 58:293-297.
7. Colvin R.A., Bush A.I., Volitakis I., Fontaine C.P., Thomas D., Kikuchi K., Holmes W.R. Insights into Zn2+ homeostasis in neurons from experimental and modeling studies. Am. J. Physiol. Cell Physiol. 2008, 294:C726-C742.
8. Cuervo A.M., Stefanis L., Fredenburg R., Lansbury P.T., Sulzer D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 2004, 305:1292-1295.
9. Ding W.Q., Liu B., Vaught J.L., Yamauchi H., Lind S.E. Anticancer activity of the antibiotic clioquinol. Cancer Res. 2005, 65:3389-3395.
10. Ding W.Q., Yu H.J., Lind S.E. Zinc-binding compounds induce cancer cell death via distinct modes of action. Cancer Lett. 2008, 271:251-259.
11. Hara T., Nakamura K., Matsui M., Yamamoto A., Nakahara Y., Suzuki-Migishima R., Yokoyama M., Mishima K., Saito I., Okano H., Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006, 441:885-889.
12. Hwang J.J., Kim H.N., Kim J., Cho D.H., Kim M.J., Kim Y.S., Kim Y., Park S.J., Koh J.Y. Zinc(II) ion mediates tamoxifen-induced autophagy and cell death in MCF-7 breast cancer cell line. Biometals 2010, 23:997-1013.
13. Klionsky D.J. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat. Rev. Mol. Cell Biol. 2007, 8:931-937.
14. Koh J.Y., Choi D.W. Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Methods. 1987, 20:83-90.
15. Komatsu M., Waguri S., Chiba T., Murata S., Iwata J., Tanida I., Ueno T., Koike M., Uchiyama Y., Kominami E., Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006, 441:880-884.
16. Lannfelt L., Blennow K., Zetterberg H., Batsman S., Ames D., Harrison J., Masters C.L., Targum S., Bush A.I., Murdoch R., Wilson J., Ritchie C.W. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2008, 7:779-786.
17. Lee J.Y., Cole T.B., Palmiter R.D., Suh S.W., Koh J.Y. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc. Natl Acad. Sci. USA 2002, 99:7705-7710.
18. Lee J.Y., Friedman J.E., Angel I., Kozak A., Koh J.Y. The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol. Aging 2004, 25:1315-1321.
19. Lee S.J., Cho K.S., Koh J.Y. Oxidative injury triggers autophagy in astrocytes: the role of endogenous zinc. Glia 2009, 57:1351-1361.
20. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 2004, 6:463-477.
21. Levine B., Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008, 132:27-42.
22. Maret W., Vallee B.L. Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc. Natl Acad. Sci. USA 1998, 95:3478-3482.
23. McCarthy K.D., de Vellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J. Cell Biol. 1980, 85:890-902.
24. Mizushima N., Klionsky D.J. Protein turnover via autophagy: implications for metabolism. Annu. Rev. Nutr. 2007, 27:19-40.
25. Pickford F., Masliah E., Britschgi M., Lucin K., Narasimhan R., Jaeger P.A., Small S., Spencer B., Rockenstein E., Levine B., Wyss-Coray T. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Invest. 2008, 118:2190-2199.
26. Ravikumar B., Duden R., Rubinsztein D.C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Genet. 2002, 11:1107-1117.
27. Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O'Kane C.J., Rubinsztein D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 2004, 36:585-595.
28. Ritchie C.W., Bush A.I., Mackinnon A., Macfarlane S., Mastwyk M., MacGregor L., Kiers L., Cherny R., Li Q.X., Tammer A., Carrington D., Mavros C., Volitakis I., Xilinas M., Ames D., Davis S., Beyreuther K., Tanzi R.E., Masters C.L. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch. Neurol. 2003, 60:1685-1691.
29. Ross C.A., Poirier M.A. Protein aggregation and neurodegenerative disease. Nat. Med. 2004, 10(Suppl):S10-S17.
30. Sarkar S., Ravikumar B., Floto R.A., Rubinsztein D.C. Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ. 2009, 16:46-56.
31. Schaumburg H.H. Experimental and clinical neurotoxicology 2000, Oxford University Press, New York.
32. Spilman P., Podlutskaya N., Hart M.J., Debnath J., Gorostiza O., Bredesen D., Richardson A., Strong R., Galvan V. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS ONE 2010, 5:e9979.
33. Tateishi J. Subacute myelo-optico-neuropathy: clioquinol intoxication in humans and animals. Neuropathology 2000, 20(Suppl):S20-S24.
34. Tsubaki T., Honma Y., Hoshi M. Neurological syndrome associated with clioquinol. Lancet 1971, 1:696-697.
35. Webb J.L., Ravikumar B., Atkins J., Skepper J.N., Rubinsztein D.C. Alpha-Synuclein is degraded by both autophagy and the proteasome. J. Biol. Chem. 2003, 278:25009-25013.
36. Yu H., Zhou Y., Lind S.E., Ding W.Q. Clioquinol targets zinc to lysosomes in human cancer cells. Biochem. J. 2009, 417:133-139.