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Chromium III Histidinate Exposure Modulates Gene Expression in HaCaT Human Keratinocytes Exposed to Oxidative Stress

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Abstract

While the toxicity of hexavalent chromium is well established, trivalent chromium is an essential nutrient involved in insulin and glucose homeostasis. To study the antioxidant effects of Cr(III)His, cDNA arrays were used to investigate the modulation of gene expression by trivalent chromium histidinate (Cr(III)His) in HaCaT human keratinocytes submitted to hydrogen peroxide (H2O2). Array was composed by a set of 81 expressed sequences tags (ESTs) essentially represented by antioxidant and DNA repair genes. HaCaT were preincubated for 24 h with 50 μM Cr(III)His and were treated with 50 μM H2O2. Total RNAs were isolated immediately or 6 h after the stress. In Cr(III)His preincubated cells, transcripts related to antioxidant family were upregulated (glutathione synthetase, heme oxygenase 2, peroxiredoxin 4). In Cr(III)His preincubated cells and exposed to H2O2, increased expressions of polymerase delta 2 and antioxidant transcripts were observed. Biochemical methods performed in parallel to measure oxidative stress in cells showed that Cr(III)His supplementation before H2O2 stress protected HaCaT from thiol groups decrease and thiobarbituric acid reactive substances increase. In summary, these results give evidence of antioxidant gene expression and antioxidant protection in HaCaT preincubated with Cr(III)His and help to explain the lack of toxicity reported for Cr(III)His.

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Abbreviations

8-oxodGuo:

8-Oxo-7-8-dihydro-2′-deoxyguanosine

ACTB:

Actin, beta

ANOVA:

Analysis of variance

Cr:

Chromium

Cr(III):

Trivalent chromium

Cr(III)His:

Trivalent chromium histidinate

Cr(VI):

Hexavalent chromium

DMSO:

Dimethylsulfoxide

DTNB:

5,5′-Dithio-Bis (2-nitrobenzoic acid)

ECM:

Extracellular matrix

ESTs:

Expressed sequence tags

GADD45A:

Growth arrest and DNA-damage-inducible alpha

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GCLM:

Glutamate-cysteine ligase, modifier subunit

GPX1:

Glutathione peroxidase 1

GSH:

Glutathione

GSR:

Glutathione reductase

GSS:

Glutathione synthetase

GST:

Glutathione S-transferase

H2O2 :

Hydrogen peroxide

HMOX2:

Heme oxygenase 2

IKBIA:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

MMP2:

Matrix metallopeptidase 2

MTT:

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

NAC:

N-acetyl cysteine

NER:

Nucleotide excision repair

NFKB1:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

NHEJ:

Non-homologous end-joining

PBS:

Phosphate-buffered saline

PCR:

Polymerase chain reaction

PLA2G5:

Phospholipase A2, group V

POLD2:

Polymerase delta 2

PRDX4:

Peroxiredoxin 4

ROS:

Reactive oxygen species

RPL32:

Ribosomal protein L32

SE:

Standard error

-SH:

Thiol groups

SHC1:

Src homology 2 domain containing transforming protein 1

SOD1:

Superoxide dismutase 1

TBARS:

Thiobarbituric acid reactive substances

TXN:

Thioredoxin

XPC:

Xeroderma pigmentosum C

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Acknowledgements

This study was part of a US Department of Agriculture funded study entitled “Insulin potentiating compounds and antioxidant nutrients in the prevention and alleviation of glucose intolerance and diabetes” and the International Agreement between laboratories from Joseph Fourier University, Grenoble, France and the Beltsville Human Nutrition Research Center entitled “Naturally Occurring Insulin Enhancing Factors”.

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Authors and Affiliations

  1. Département de Biologie Intégrée, Biologie Nutritionnelle, Centre Hospitalier Universitaire, BP 217, 38043, Grenoble Cedex 09, France

    Florence Hazane-Puch, Kita Valenti, François Laporte & Alain Favier

  2. LBFA, Université Joseph Fourier, Grenoble I, 38041, France

    Rachida Benaraba, Mireille Osman, Anne-Marie Roussel & Isabelle Hininger-Favier

  3. INSERM, U884, Grenoble, 38000, France

    Mireille Osman, Anne-Marie Roussel & Isabelle Hininger-Favier

  4. USDA, ARS, BHNRC, DGIL, Bldg. 307C, Rm. 222, BARC-East, Beltsville, MD, 20705-2350, USA

    Richard A. Anderson

  5. LBFA (Laboratoire de Bioénergétique Fondamentale et Appliquée), UFR Pharmacie, Domaine de la Merci, 38700, La Tronche, France

    Isabelle Hininger-Favier

Authors
  1. Florence Hazane-Puch
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  2. Rachida Benaraba
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  3. Kita Valenti
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  7. Richard A. Anderson
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  8. Anne-Marie Roussel
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  9. Isabelle Hininger-Favier
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Corresponding author

Correspondence to Isabelle Hininger-Favier.

Additional information

Chromium–histidine complexes as nutrient supplements, serial no. 09/414,645, is a patent of the USDA and R.A. Anderson is one of the inventors.

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Hazane-Puch, F., Benaraba, R., Valenti, K. et al. Chromium III Histidinate Exposure Modulates Gene Expression in HaCaT Human Keratinocytes Exposed to Oxidative Stress. Biol Trace Elem Res 137, 23–39 (2010). https://doi.org/10.1007/s12011-009-8557-9

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  • DOI: https://doi.org/10.1007/s12011-009-8557-9

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