Nrf2-Keap1 signaling in oxidative and reductive stress

Biochim Biophys Acta Mol Cell Res. 2018 May;1865(5):721-733. doi: 10.1016/j.bbamcr.2018.02.010. Epub 2018 Feb 27.


Nrf2 and its endogenous inhibitor, Keap1, function as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress. Sequestered by cytoplasmic Keap1 and targeted to proteasomal degradation in basal conditions, in case of oxidative stress Nrf2 detaches from Keap1 and translocates to the nucleus, where it heterodimerizes with one of the small Maf proteins. The heterodimers recognize the AREs, that are enhancer sequences present in the regulatory regions of Nrf2 target genes, essential for the recruitment of key factors for transcription. In the present review we briefly introduce the Nrf2-Keap1 system and describe Nrf2 functions, illustrate the Nrf2-NF-κB cross-talk, and highlight the effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress.

Keywords: Antioxidant system; Autophagy; Nrf2/Keap1; Nrf2/NF-κB cross-talk; Oxidative stress; Reductive stress; Striated muscle.

Publication types

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

MeSH terms

  • Cell Nucleus / genetics
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / genetics*
  • Maf Transcription Factors / genetics
  • NF-E2-Related Factor 2 / genetics*
  • NF-kappa B / genetics
  • Oxidation-Reduction
  • Oxidative Stress / genetics*
  • Signal Transduction


  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • Maf Transcription Factors
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human