Curcumin alters EpRE and AP‐1 binding complexes and elevates glutamate‐cysteine ligase gene expression

• DOI: 10.1096/fj.02-0566fje
• Publication Date: 2003-03-11T22:42:07Z
• Authors: Dale A. Dickinson; Karen E. Iles; Hongqiao Zhang; Volker Blank; Henry Jay Forman
• Keywords: Cell Nucleus; Transcriptional Activation; 2. Zero hunger; 0303 health sciences; Binding Sites; Curcumin; Macromolecular Substances; NF-E2-Related Factor 2; Proto-Oncogene Proteins c-jun; Glutamate-Cysteine Ligase; Nuclear Proteins; Response Elements; Glutathione; MafK Transcription Factor; DNA-Binding Proteins; Repressor Proteins; Transcription Factor AP-1; 03 medical and health sciences; Gene Expression Regulation; Trans-Activators; Phosphorylation

Dietary use of curcumin, the active component of tumeric, one of the most widely used spices, is linked to several beneficial health effects, although the underlying molecular mechanisms remain largely unknown. Correlations have been established between curcumin exposure and increases in enzymes for glutathione synthesis, particularly glutamate-cysteine ligase (GCL), and metabolism as well as glutathione content, suggesting the eliciting of an adaptive response to stress. In this study, using HBE1 cells, we found that the mechanism of curcumin-induced GCL elevation occurred via transcription of the two Gcl genes. Gcl transcription has been shown in several systems to be mediated through binding of transcription factor complexes to TRE and EpRE elements. Studies herein showed that curcumin caused modest but sustained increases in binding of proteins to DNA sequences for both cis elements but, more importantly, altered the compositions and nuclear content of proteins in these complexes. Curcumin exposure increased JunD and c-Jun content in AP-1 complexes and increased JunD while decreasing MafG/MafK in EpRE complexes. Thus, the beneficial effects elicited by curcumin appear to be due to changes in the pool of transcription factors that compose EpRE and AP-1 complexes, affecting gene expression of GCL and other phase II enzymes.