title: The pesticide deltamethrin increases free radical production and promotes nuclear translocation of the stress response transcription factor Nrf2 in rat brain.
abstract: The transcription factor NF-E2-related factor 2 (Nrf2) plays a critical role in the mammalian response to chemical and oxidative stress through induction of phase II detoxification enzymes and oxidative stress response proteins. We reported that Nrf2 expression was activated by deltamethrin (DM), a prototype of the widely used Parathyroid pesticides, in PC12 cells. However, no study has examined Nrf2 nuclear translocation and free radical production, two hallmarks of oxidative stress, in the mammalian brain in vivo. To this end, we examined translocation of Nrf2 and production of free radicals in rat brain exposed to DM. Indeed, DM initiated nuclear translocation of Nrf2 in a dose-dependent manner. Furthermore, Nrf2 translocation was accompanied by the expression of heme oxygenase-1 gene, an Nrf2-regulated gene linked to free radical production. Deltamethrin exposure promoted free radical formation in rat brain and reactive oxygen species generation in PC12 cells. Translocation of Nrf2 may be a response to DM-dependent induction of free radicals and DM may act as a mammalian neurotoxin by initiating oxidative stress.
authors.affiliation: Department of Occupational and Environmental Health, Institution of Environmental and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fuzhou, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Li
authors.forename: S Y
authors.initials: SY
authors.lastname: Wu
authors.forename: Q
authors.initials: Q
authors.lastname: Ma
authors.forename: N
authors.initials: N
authors.lastname: Shi
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism*; D005786:Gene Expression Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D009570:Nitriles / Q000633:toxicity*; D018384:Oxidative Stress; D016716:PC12 Cells; D011722:Pyrethrins / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005609:Free Radicals; D007306:Insecticides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D009570:Nitriles; D011722:Pyrethrins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C017180:decamethrin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat