Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles

Details

• Personal Author:
  Burks T ; Fadeel B ; Garcia-Bennett A ; Gogvadze V ; Johansson K ; Kagan VE ; Karlsson HL ; Li J ; Mathur S ; Morgenstern R ; Muhammed M ; Shi J ; Uheida A ; Xiao L
• Description:
  Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Enzymes Lipids Occupational Health Oxidants Safety Toxicology
• Keywords:
  Author Keywords: Engineered Nanoparticles Biological Effects Cytotoxic Effects Cytotoxicity Enzyme Activity Lipid Peroxidation Microsomal Glutathione Transferase 1 Nanomaterials Nanoparticles Nanotoxicology Oxidative Processes Oxidative Stress

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• ISSN:
  1936-0851
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  6
• Issue:
  3
• NIOSHTIC Number:
  nn:20053280
• Citation:
  ACS Nano 2012 Mar; 6(3):1925-1938
• Contact Point Address:
  Bengt Fadeel, Institute of Environmental Medicine, Karolinska Institutet, 17177 Stockholm, Sweden
• Email:
  bengt.fadeel@ki.se
• CAS Registry Number:
  Ceria (CAS RN 1306-38-3) ; Silica (CAS RN 7631-86-9) ; Tin oxide (SnO) (CAS RN 21651-19-4) ; Titania (CAS RN 13463-67-7) ; Zinc oxide (ZnO) (CAS RN 1314-13-2)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  ACS Nano
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ad7ed6877e9aa2937b0a68d23d6fbb90051b2286ddc788db2ab90566d83a9c39c86ea5a8493e42d55688a9e7635e8d85ad15e1e436684cc99d2ecafaaef0e54f
• Download URL:
  https://stacks.cdc.gov/view/cdc/216071/cdc_216071_DS1.pdf
• File Type:
  [PDF - 1.76 MB ]