Transcription factor Nrf2 activation by deltamethrin in PC12 cells: Involvement of ROS.
Activation of transcription factor NF-E2-related factor 2 (Nrf2) is a key initiation step in the cellular protection against a broad range of chemical oxidative stresses. To gain insights into dopaminergic cell responses to pesticides, the present study was conducted to examine the effects of deltamethrin (DM), a prototype of widely used pyrithroid pesticides, on the activation and expression of Nrf2 in PC12 rat adrenal pheochromocytoma cells as a dopaminergic cell model. We found, for the first time, that DM enhanced cellular expression of Nrf2 at the transcriptional and protein levels and activated expression of Nrf2-regulated genes in these cells. In addition, DM exposure caused nuclear accumulation of Nrf2 in association with downstream activation of Nrf2-mediated oxidative response genes, such as heme oxygenase-l (HO-1) and gamma-glutamylcysteine synthetase catalytic heavy subunit (GCSh). Furthermore, when cells were pretreated with N-acetyl cysteine (NAC), a scavenger of reactive oxygen species (ROS), DM-induced Nrf2 signaling was suppressed. These results indicate that ROS is the mediator of nuclear Nrf2 accumulation. Taken together, these data clearly show that DM increases Nrf2 expression and activity and that ROS is one of the mediators of this process.
Li
Huang-Yuan
HY
Department of Occupational and Environmental Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, Fuzhou 350004, China.
Wu
Si-Ying
SY
Shi
Nian
N
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D016716:PC12 Cells; D011722:Pyrethrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; D009570:Nitriles; D011722:Pyrethrins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C017180:decamethrin; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; D000111:Acetylcysteine