Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/21/2009
Publication Date: 5/10/2010
Citation: Puch, F., Benaraba, R., Hazane, F., Valenti, K., Osman, M., Laporte, F., Favier, A., Anderson, R.A., Roussel, A., Hininger, I. 2010. Chromium III histidinate exposure modulates antioxidant gene expression in HaCaT human keratinocytes exposed to oxidative stress. Biological Trace Element Research. (137):23-39.
Interpretive Summary: Trivalent chromium (Cr(III)) is an essential trace element that improves the function of insulin and is required for normal sugar and fat metabolism. Numerous studies have shown beneficial effects of consuming chromium on glucose utilization and lipid profiles of people with impaired glucose tolerance or type-2 diabetes. Chromium (III) is taken as a dietary supplement and has been reported to increase fat loss and promote lean mass. The aim of this work was to assess a possible molecular mechanism of these effects by investigating changes in activity of antioxidant genes when chromium histidinate was added to human skin cells placed in solutions with substances that create oxidative stress. We identified the genes in the skin cells involved and measured various signs of oxidative stress. When cells were pre-incubated with chromium histidinate before they were exposed to the oxidative stress, increased activity in genes involved in oxidative repair and antioxidant defense was observed. These results were associated with protective antioxidant effects. In summary, these results show increases in activity of antioxidant genes in cells exposed to chromium histidinate and help explain the antioxidant effects of chromium histidinate. This work should be of interest not only to the scientific community but also to people whose dietary choices may lead to adverse effects on the body’s antioxidant defense system.
Technical Abstract: While the toxicity of hexavalent chromium is well established, trivalent Cr (Cr(III)) is an essential nutrient involved in insulin and glucose homeostasis. Recently, antioxidant effects of chromium (III) histidinate (Cr(III)His) were reported in HaCaT human keratinocytes exposed to oxidative stress. The aim of this work was to assess a possible molecular mechanism of these effects by investigating the modulation of antioxidant gene expression by Cr(III)His in HaCaT human keratinocytes submitted to oxidative stress. We used cDNA microarray to identify common batteries of genes implicated and routine methods were performed to measure oxidative stress parameters in the cells as thiobarbituric acid reactants (TBARS) and thiol groups (SH). HaCaT keratinocytes were pre-incubated with 50 µM Cr(III)His before and after H2O2 treatment (50µM). Total RNA was isolated immediately after stress or after 6h. Gene modulation was studied as a function of H2O2 and/or Cr(III)His by multiple analyses (n=4). In Cr(III)His-exposed cells, transcripts related to the antioxidant family were up-regulated (AOE372, GSS, SCH1) as POLD2 and FOSB. When cells were pre-incubated with Cr(III)His before H2O2, an increased expression in genes implicated in oxidative repair (POLD2) and antioxidant defense (GSS) was observed, whereas the SOD2 transcript was down-regulated. These results were associated with protective antioxidant effects assessed by a decrease in TBARS and an increase in SH to combat oxidative stress. In summary, these results show up-regulation in antioxidant gene expression in cells exposed to Cr(III)His and help explain the antioxidant effects and the lack of toxicity reported for chromium histidinate.