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Oxidative Stress Induced by Cadmium in the C6 Cell Line: Role of Copper and Zinc

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Abstract

In this report, we have investigated the role of copper (Cu) and zinc (Zn) in oxidative stress induced by cadmium (Cd) in C6 cells. Cells were exposed to 20 μM Cd, 500 μM Cu, and 450 μM Zn for 24 h. Then, toxic effects, cellular metals levels, oxidative stress parameters, cell death, as well as DNA damage were evaluated. Cd induced an increase in cellular Cd, Cu, and Zn levels. This results not only in the inhibition of GSH-Px, GRase, CAT, and SOD activities but also in ROS overproduction, oxidative damage, and apoptotic cell death not related to Cu and Zn mechanisms. The thiol groups and GSH levels decreased, whereas the lipid peroxidation and DNA damage increased. The toxicity of Zn results from the imbalance between the inhibition of antioxidant activities and the induction of MT synthesis. The increase in Cu and Zn levels could be explained by the disruption of specific transporter activities, Cd interference with signaling pathways, and metal displacement. Our results suggest that the alteration of Cu and Zn homeostasis is involved in the oxidative stress induced by Cd.

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Abbreviations

CAT:

Catalase

Cd:

Cadmium

Cu:

Copper

Zn:

Zinc

FBS:

Fetal bovine serum

GSH-Px:

Glutathione peroxydase

GRase:

Glutathione reductase

GSH:

Reduced glutathione

GSSG:

Oxized glutathione

MDA:

Malondialdehyde

MT:

Metallothioneins

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

ROS:

Reactive oxygen species

DMEM:

Dulbecco’s modified Eagle’s medium

BCA:

Bicinchoninic acid

BHT:

3,5-Di-tert-4butylhydroxytoluene

DMSO:

Dimethyl sulfoxide

DTNB:

5,5′-Dithionitrobenzoic acid

EDTA:

Ethylenediamine tetraacetic acid

NADPH:

Nicotinamide dinucleotide phosphate

PBS:

Phosphate-buffered saline

TBARs:

Thiobarbituric acid reactants

TNB:

5-Thio-2-nitrobenzoic acid

ABTS:

2,2′-Azino-di-[3-ethylbenzthiazoline-sulfonate(6)]

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Acknowledgments

We thank Malika Kadri-Dakir, Sandra Grange, and Angèle Krawiec for their technical assistance.

Author information

Authors and Affiliations

  1. INAC/SCIB UMR-E3 CEA/UJF, Laboratoire Lésions des Acides Nucléiques, CEA-Grenoble, 17 rue des Martyrs, 38054, Grenoble Cedex 9, France

    Yves Nzengue, Walid Rachidi & Alain Favier

  2. Oligoéléments et Résistance au Stress Oxydant induit par les Xénobiotiques (ORSOX), EA-3776, LRC CEA 8M, UFR de Pharmacie, Université Joseph Fourier, Domaine de La Merci, 38700, La Tronche, France

    Yves Nzengue, Régine Steiman & Pascale Guiraud

  3. Laboratoire Signalisation et Infections virales, Centre Hospitalier de l’Université de Montréal (CRCHUM), PEA 416, 264 René-Levesque, Montréal, QC, H2X 1P1, Canada

    Yves Nzengue

  4. Départment de Biochimie, Faculté de Médicine, Université de Montréal, Montréal, QC, Canada

    Yves Nzengue

  5. Département des Sciences Médicales et Laboratoire de Biochimie et Génétique Moléculaire (LBGM, EA 2526), UFR des Sciences et Technologies, Université de la Réunion, 15 avenue René Cassin, BP 7151, 97715, Saint Denis Messag Cedex 9, France

    Pascale Guiraud

Authors
  1. Yves Nzengue
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  2. Régine Steiman
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  3. Walid Rachidi
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  4. Alain Favier
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  5. Pascale Guiraud
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Corresponding author

Correspondence to Yves Nzengue.

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Nzengue, Y., Steiman, R., Rachidi, W. et al. Oxidative Stress Induced by Cadmium in the C6 Cell Line: Role of Copper and Zinc. Biol Trace Elem Res 146, 410–419 (2012). https://doi.org/10.1007/s12011-011-9265-9

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  • DOI: https://doi.org/10.1007/s12011-011-9265-9

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