The pathways and molecular mechanisms regulating Nrf2 activation in response to chemical stress

摘要: The induction of many antioxidant and phase II drug-metabolizing enzymes by phenolic antioxidants electrophilic compounds is regulated at the transcriptional level. response to these mediated cis-acting element (ARE) found in promoter encoding genes. transcription factor NF-E2-related 2, or Nrf2, has emerged as central protein that binds ARE activate gene transcription. Data from studies indicate Nrf2 constitutively ubiquitously expressed a number tissues cell lines thus responsible for low-level expression its target genes observed under physiological conditions. However, cells exposed oxidative stress, activity increased, further driving activation whose essential control cellular redox homeostasis. Recent suggest involves coordinated process multiple levels. believed be repressed through binding cytoskeleton-associated Keap1, mechanisms interfere with this interaction. Activation also been demonstrated dependent on mediate stabilization. In review, controlling reported recent will examined discussed, particular emphasis those affecting stability molecular