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Iron-dependent formation of reactive oxygen species and glutathione depletion after accumulation of magnetic iron oxide nanoparticles by oligodendroglial cells

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Abstract

Magnetic iron oxide nanoparticles (IONP) are currently used for various neurobiological applications. To investigate the consequences of a treatment of brain cells with such particles, we have applied dimercaptosuccinate (DMSA)-coated IONP that had an average hydrodynamic diameter of 60 nm to oligodendroglial OLN-93 cells. After exposure to 4 mM iron applied as DMSA–IONP, these cells increased their total specific iron content within 8 h 600-fold from 7 to 4,200 nmol/mg cellular protein. The strong iron accumulation was accompanied by a change in cell morphology, although the cell viability was not compromized. DMSA–IONP treatment caused a concentration-dependent increase in the iron-dependent formation of reactive oxygen species and a decrease in the specific content of the cellular antioxidative tripeptide glutathione. During a 16 h recovery phase in IONP-free culture medium following exposure to DMSA–IONP, OLN-93 cells maintained their high iron content and replenished their cellular glutathione content. These data demonstrate that viable OLN-93 cells have a remarkable potential to deal successfully with the consequences of an accumulation of large amounts of iron after exposure to DMSA–IONP.

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Abbreviations

AA:

Amino acids

ANOVA:

Analysis of variance

BSO:

Buthionine sulfoximine

DMEM:

Dulbecco’s modified Eagle’s medium

DMSA:

Dimercaptosuccinate

FCS:

Fetal calf serum

GSH:

Glutathione

GSSG:

Glutathione disulfide

GSx:

Total glutathione

IB:

Incubation buffer

IONP:

Iron oxide nanoparticles

LDH:

Lactate dehydrogenase

PBS:

Phosphate buffered saline

Phen:

Phenanthroline

PI:

Propidium iodide

ROS:

Reactive oxygen species

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Acknowledgments

The authors would like to thank the Forschungsförderung of the University Bremen for financial support. Michaela C. Hohnholt is a member of the graduate school nanoToxCom. The authors would like to thank Mark Geppert (University of Bremen) for providing the DMSA-coated and citrate-coated IONP and Professor Christiane Richter-Landsberg (University of Oldenburg) for providing the OLN-93 cells.

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Authors and Affiliations

  1. Centre for Biomolecular Interactions Bremen, University of Bremen, P.O. Box 330440, 28334, Bremen, Germany

    Michaela C. Hohnholt & Ralf Dringen

  2. Centre for Environmental Research and Sustainable Technology, Leobener Straße, 28359, Bremen, Germany

    Michaela C. Hohnholt & Ralf Dringen

  3. School of Psychology & Psychiatry, Monash University, Wellington Rd., Clayton, VIC, 3800, Australia

    Ralf Dringen

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  1. Michaela C. Hohnholt
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Correspondence to Ralf Dringen.

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Hohnholt, M.C., Dringen, R. Iron-dependent formation of reactive oxygen species and glutathione depletion after accumulation of magnetic iron oxide nanoparticles by oligodendroglial cells. J Nanopart Res 13, 6761–6774 (2011). https://doi.org/10.1007/s11051-011-0585-7

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