Dexamethasone induces human glutathione S transferase alpha 1 (hGSTA1) expression through the activation of glucocorticoid receptor (hGR).

The glutathione S transferases (GSTs) are a superfamily of isoenzymes that play an important role in xenobiotic and endobiotic detoxification, cellular protection from oxidative stress and modulation of signalling pathways. Human GSTA1 (hGSTA1), a cytosolic isoform, is the most abundant GST in the liver and is involved in the metabolism of carcinogenic compounds, chemotherapeutic agents and lipid peroxidation products. However, the molecular mechanism underlying the regulation of hGSTA1 expression is not well understood. Therefore, the aim of the present study was to better understand the regulation of hGSTA1 gene expression. Putative response elements for several nuclear receptors, including the glucocorticoid receptor (GR), have been identified at the hGSTA1 gene promoter located at -896bp, -863bp and -727bp from the transcription start site. After dexamethasone (DEX) treatment, the GR induces hGSTA1 expression at the transcriptional level. The characterisation of this effect reveals that the GR binds to several glucocorticoid response elements (GREs) located at the hGSTA1 gene promoter. This interaction also results in the transactivation of the hGSTA1 gene promoter together with an increase of the hGSTA1 mRNA levels as well as the protein and activity levels in HepG2 cells. Together, the present results suggest that glucocorticoids have the potential to alter the xenobiotic and endobiotic metabolism mediated by hGSTA1.