Human glutamate cysteine ligase gene regulation through the electrophile response element

Free Radic Biol Med. 2004 Oct 15;37(8):1152-9. doi: 10.1016/j.freeradbiomed.2004.06.011.


Glutathione (GSH) is the primary nonprotein thiol in the cell. It has many important roles in cell function, including regulating redox-dependent signal transduction pathways. The content of GSH within the cell varies with stress. In many cases, a process involving GSH synthesis results in adaptation to subsequent stressors. Sustained increases in GSH content are controlled primarily through induction of two genes, Gclc and Gclm, leading to the synthesis of the rate-limiting enzyme for GSH synthesis, glutamate cysteine ligase. Each of these genes in humans has a number of putative enhancer elements in their promoters. Overall, the most important element in both Gclc and Gclm expression is the electrophile response element. We review the evidence that has led to this conclusion and the implications for the redox-dependent regulation of this critical intracellular antioxidant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Curcumin / pharmacology
  • DNA-Binding Proteins / metabolism
  • Enzyme Induction / drug effects
  • Genes
  • Glutamate-Cysteine Ligase / biosynthesis
  • Glutamate-Cysteine Ligase / genetics*
  • Humans
  • I-kappa B Proteins / metabolism
  • Lipid Metabolism
  • Lipids / chemistry
  • NF-E2-Related Factor 2
  • NF-kappa B / metabolism
  • Oxidation-Reduction
  • Promoter Regions, Genetic / genetics
  • Response Elements / genetics*
  • Signal Transduction
  • Trans-Activators / metabolism
  • Transcription, Genetic


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Lipids
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Trans-Activators
  • Glutamate-Cysteine Ligase
  • Curcumin