Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase gene expression.
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.
Dickinson
Dale A
DA
Department of Environmental Health Sciences, School of Public Health, and Center for Free Radical Biology, University of Alabama at Birmingham, 35294-0022, USA.
Iles
Karen E
KE
Zhang
Hongqiao
H
Blank
Volker
V
Forman
Henry Jay
HJ
D001665:Binding Sites; D002467:Cell Nucleus / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000032:analysis; D005786:Gene Expression Regulation; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis / Q000235:genetics*; D005978:Glutathione / Q000096:biosynthesis; D046911:Macromolecular Substances; D050985:MafK Transcription Factor; D051267:NF-E2-Related Factor 2; D009687:Nuclear Proteins / Q000032:analysis; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis; D020218:Response Elements; D015534:Trans-Activators / Q000032:analysis; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D050985:MafK Transcription Factor; D051267:NF-E2-Related Factor 2; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D003474:Curcumin