Original scientific paper
https://doi.org/10.2478/10004-1254-64-2013-2251
Effect of Glutathione Depletion on Nrf2/ARE Activation by Deltamethrin in PC12 Cells
Huangyuan Li
; Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical Univ
Siying Wu
; Department of Epidemiology and Health Statistics, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical University, China
Junnian Chen
; Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical Univ
Bo Wang
; Department of Occupational and Environmental Health, Fujian Province Key lab of Environment and Health, Institution of Environment and Health, Major Subject of Environment and Health of Fujian Key Universities, School of Public Health, Fujian Medical Univ
Nian Shi
; Department of Health Toxicology, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, China
Abstract
Transcription factor NF-E2-related factor 2 (Nrf2) is important for cell protection against chemical-induced oxidative stress. Previously, we have reported that in PC12 cells, Nrf2 can be triggered by deltamethrin (DM), a commonly used pyrethroid insecticide. Molecular mechanisms behind Nrf2 activation by DM are still unclear. Here we studied the effects of cell glutathione (GSH) depletion on Nrf2 activation by DM. We found that DM enhanced Nrf2 expression at the mRNA and protein levels and increased nuclear Nrf2 levels. Activation of Nrf2 was associated with activation of its downstream targets, such as heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit (GCLC). In contrast, DL-buthionine-[S,R]- sulfoximine (BSO), a known GSH-depleting agent, did not increase Nrf2 protein expression or cause its nuclear accumulation. However, pre-treatment with BSO triggered mRNA expression of HO-1 and GCLC. Furthermore, BSO pre-treatment suppressed DM-induced Nrf2 upregulation and activation and lowered mRNA expression of HO-1 and GCLC upon DM treatment. These data demonstrate that GSH depletion is not necessary for the activation of Nrf2/ARE by DM in PC12 cells, and that GCLC and HO-1 expression can increase through other signalling pathways.
Keywords
BSO; DL-buthionine-[S,R]-sulfoximine; glutamate cysteine ligase catalytic subunit; GCLC; heme oxygenase; HO-1; pyrethroid insecticide
Hrčak ID:
98687
URI
Publication date:
20.3.2013.
Visits: 2.872 *