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Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans.

Abstract

Zinc oxide nanoparticles (ZnONPs) are used in large quantities by the cosmetic, food and textile industries. Here we exposed Caenorhabditis elegans wild-type and a metal sensitive triple knockout mutant (mtl-1;mtl-2;pcs-1) to ZnONPs (0-50mg/L) to study strain and exposure specific effects on transcription, reactive oxygen species generation, the biomolecular phenotype (measured by Raman microspectroscopy) and key endpoints of the nematode life cycle (growth, reproduction and lifespan). A significant dissolution effect was observed, where dissolved ZnO constituted over 50% of total Zn within a two day exposure to the test medium, suggesting that the nominal exposure to pure ZnONPs represents in vivo, at best, a mixture exposure of ionic zinc and nanoparticles. Nevertheless, the analyses provided evidence that the metallothioneins (mtl-1 and mtl-2), the phytochelatin synthase (pcs-1) and an apoptotic marker (cep-1) were transcriptionally activated. In addition, the DCFH-DA assay provided in vitro evidence of the oxidative potential of ZnONPs in the metal exposure sensitive triple mutant. Raman spectroscopy highlighted that the biomolecular phenotype changes significantly in the mtl-1;mtl-2;pcs-1 triple knockout worm upon ZnONP exposure, suggesting that these metalloproteins are instrumental in the protection against cytotoxic damage. Finally, ZnONP exposure was shown to decrease growth and development, reproductive capacity and lifespan, effects which were amplified in the triple knockout. By combining diverse toxicological strategies, we identified that individuals (genotypes) housing mutations in key metalloproteins and phytochelatin synthase are more susceptible to ZnONP exposure, which underlines their importance to minimize ZnONP induced toxicity.

Authors+Show Affiliations

MRC-HPA Centre for Environment & Health, School of Biomedical Sciences, King's College London, London, UK.Centre for Ecology and Hydrology, Maclean Building, Wallingford, Oxfordshire OX10 8BB, UK.Department of Materials, Hirsch Building, University of Oxford, Kidlington OX5 1PF, UK.Centre for Ecology and Hydrology, Maclean Building, Wallingford, Oxfordshire OX10 8BB, UK.MRC-HPA Centre for Environment & Health, School of Biomedical Sciences, King's College London, London, UK.Centre for Ecology and Hydrology, Maclean Building, Wallingford, Oxfordshire OX10 8BB, UK.MRC-HPA Centre for Environment & Health, School of Biomedical Sciences, King's College London, London, UK. Electronic address: stephen.sturzenbaum@kcl.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24333255

Citation

Polak, Natasa, et al. "Metalloproteins and Phytochelatin Synthase May Confer Protection Against Zinc Oxide Nanoparticle Induced Toxicity in Caenorhabditis Elegans." Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, vol. 160, 2014, pp. 75-85.
Polak N, Read DS, Jurkschat K, et al. Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans. Comp Biochem Physiol C Toxicol Pharmacol. 2014;160:75-85.
Polak, N., Read, D. S., Jurkschat, K., Matzke, M., Kelly, F. J., Spurgeon, D. J., & Stürzenbaum, S. R. (2014). Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans. Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, 160, 75-85. https://doi.org/10.1016/j.cbpc.2013.12.001
Polak N, et al. Metalloproteins and Phytochelatin Synthase May Confer Protection Against Zinc Oxide Nanoparticle Induced Toxicity in Caenorhabditis Elegans. Comp Biochem Physiol C Toxicol Pharmacol. 2014;160:75-85. PubMed PMID: 24333255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans. AU - Polak,Natasa, AU - Read,Daniel S, AU - Jurkschat,Kerstin, AU - Matzke,Marianne, AU - Kelly,Frank J, AU - Spurgeon,David J, AU - Stürzenbaum,Stephen R, Y1 - 2013/12/11/ PY - 2013/10/25/received PY - 2013/12/03/revised PY - 2013/12/04/accepted PY - 2013/12/17/entrez PY - 2013/12/18/pubmed PY - 2014/9/10/medline KW - C. elegans KW - CARS KW - Cd KW - Coherent anti-Stokes Raman spectroscopy KW - DCFH-DA KW - DLS KW - EDX KW - MT KW - Metallothionein KW - NGM KW - PBS KW - PC KW - PCA KW - Phytochelatin synthase KW - ROS KW - Raman spectroscopy KW - Reactive oxygen species KW - TEM KW - Zinc oxide nanoparticles KW - Zn KW - ZnONP KW - cadmium KW - dichlorodihydrofluoroscein diacetate KW - dynamic light spectroscopy KW - energy-dispersive X-ray spectroscopy KW - metallothionein KW - nematode growth medium KW - phosphate buffered saline KW - phytochelatin KW - principle component analysis KW - qRT-PCR KW - quantitative Real-Time polymerase chain reaction KW - reactive oxygen species KW - transmission electron microscopy KW - zinc KW - zinc oxide nanoparticles SP - 75 EP - 85 JF - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JO - Comp Biochem Physiol C Toxicol Pharmacol VL - 160 N2 - Zinc oxide nanoparticles (ZnONPs) are used in large quantities by the cosmetic, food and textile industries. Here we exposed Caenorhabditis elegans wild-type and a metal sensitive triple knockout mutant (mtl-1;mtl-2;pcs-1) to ZnONPs (0-50mg/L) to study strain and exposure specific effects on transcription, reactive oxygen species generation, the biomolecular phenotype (measured by Raman microspectroscopy) and key endpoints of the nematode life cycle (growth, reproduction and lifespan). A significant dissolution effect was observed, where dissolved ZnO constituted over 50% of total Zn within a two day exposure to the test medium, suggesting that the nominal exposure to pure ZnONPs represents in vivo, at best, a mixture exposure of ionic zinc and nanoparticles. Nevertheless, the analyses provided evidence that the metallothioneins (mtl-1 and mtl-2), the phytochelatin synthase (pcs-1) and an apoptotic marker (cep-1) were transcriptionally activated. In addition, the DCFH-DA assay provided in vitro evidence of the oxidative potential of ZnONPs in the metal exposure sensitive triple mutant. Raman spectroscopy highlighted that the biomolecular phenotype changes significantly in the mtl-1;mtl-2;pcs-1 triple knockout worm upon ZnONP exposure, suggesting that these metalloproteins are instrumental in the protection against cytotoxic damage. Finally, ZnONP exposure was shown to decrease growth and development, reproductive capacity and lifespan, effects which were amplified in the triple knockout. By combining diverse toxicological strategies, we identified that individuals (genotypes) housing mutations in key metalloproteins and phytochelatin synthase are more susceptible to ZnONP exposure, which underlines their importance to minimize ZnONP induced toxicity. SN - 1532-0456 UR - https://www.unboundmedicine.com/medline/citation/24333255/Metalloproteins_and_phytochelatin_synthase_may_confer_protection_against_zinc_oxide_nanoparticle_induced_toxicity_in_Caenorhabditis_elegans_ DB - PRIME DP - Unbound Medicine ER -