title: Dietary regulation of Keap1/Nrf2/ARE pathway: focus on plant-derived compounds and trace minerals.
abstract: It has become increasingly evident that chronic inflammation underpins the development of many chronic diseases including cancer, cardiovascular disease and type 2 diabetes. Oxidative stress is inherently a biochemical dysregulation of the redox status of the intracellular environment, which under homeostatic conditions is a reducing environment, whereas inflammation is the biological response to oxidative stress in that the cell initiates the production of proteins, enzymes, and other compounds to restore homeostasis. At the center of the day-to-day biological response to oxidative stress is the Keap1/Nrf2/ARE pathway, which regulates the transcription of many antioxidant genes that preserve cellular homeostasis and detoxification genes that process and eliminate carcinogens and toxins before they can cause damage. The Keap1/Nrf2/ARE pathway plays a major role in health resilience and can be made more robust and responsive by certain dietary factors. Transient activation of Nrf2 by dietary electrophilic phytochemicals can upregulate antioxidant and chemopreventive enzymes in the absence of actual oxidative stress inducers. Priming the Keap1/Nrf2/ARE pathway by upregulating these enzymes prior to oxidative stress or xenobiotic encounter increases cellular fitness to respond more robustly to oxidative assaults without activating more intense inflammatory NFκB-mediated responses.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road E, Guelph, Ontario, Canada N1G 2W1. astefans@uoguelph.ca.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Stefanson
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, 50 Stone Road E, Guelph, Ontario, Canada N1G 2W1. mbakovic@uoguelph.ca.
authors.forename: Marica
authors.initials: M
authors.lastname: Bakovic
mesh_terms: D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000378:metabolism*; D004032:Diet; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D064209:Phytochemicals / Q000494:pharmacology*; D010945:Plants, Edible / Q000737:chemistry; D014131:Trace Elements / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D064209:Phytochemicals; D014131:Trace Elements