Effect of Glutathione Depletion on Nrf2/ARE Activation by Deltamethrin in PC12 Cells

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.

• Publication year

  2013

• Venue

  Arhiv za Higijenu Rada i Toksikologiju

• Publication date

  2013-03-01

• Fields of study

  Biology, Medicine, Chemistry, Environmental Science

• Identifiers
  DOI 10.2478/10004-1254-64-2013-2251PMID 23585199
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Activation of Nuclear Factor Kappa B (NF- κ B) Assayed by Laser Scanning Cytometry (LSC)

  2013cited by this paper
• The pesticide deltamethrin increases free radical production and promotes nuclear translocation of the stress response transcription factor Nrf2 in rat brain

  2011cited by this paper
• Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1 defence response pathway in CD-1 mice.

  2008cited by this paper
• [Effect of deltamethrin on production of reactive oxygen species in PC12 cells].

  2008cited by this paper
• Submicromolar concentrations of 4-hydroxynonenal induce glutamate cysteine ligase expression in HBE1 cells

  2007cited by this paper
• Transcription factor Nrf2 activation by deltamethrin in PC12 cells: Involvement of ROS.

  2007cited by this paper
• Oxidative and Electrophilic Stresses Activate Nrf2 through Inhibition of Ubiquitination Activity of Keap1

  2006cited by this paper
• Nrf2 Possesses a Redox-insensitive Nuclear Export Signal Overlapping with the Leucine Zipper Motif*

  2005cited by this paper
• Specific Patterns of Electrophile Adduction Trigger Keap1 Ubiquitination and Nrf2 Activation*

  2005influential reference
• Nuclear Import and Export Signals in Control of Nrf2*

  2005cited by this paper
• Increased expression of heat shock proteins in rat brain during aging: relationship with mitochondrial function and glutathione redox state.

  2004cited by this paper
• Regulation of Heme Oxygenase-1 Expression through the Phosphatidylinositol 3-Kinase/Akt Pathway and the Nrf2 Transcription Factor in Response to the Antioxidant Phytochemical Carnosol*

  2004cited by this paper
• Activation of hepatic Nrf2 in vivo by acetaminophen in CD‐1 mice

  2004influential reference
• Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex

  2004cited by this paper
• Increased Protein Stability as a Mechanism That Enhances Nrf2-mediated Transcriptional Activation of the Antioxidant Response Element

  2003cited by this paper
• Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway.

  2003cited by this paper
• Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element.

  2003cited by this paper
• Coordinate Regulation of Glutathione Biosynthesis and Release by Nrf2-Expressing Glia Potently Protects Neurons from Oxidative Stress

  2003cited by this paper
• Modulation of Gene Expression by Cancer Chemopreventive Dithiolethiones through the Keap1-Nrf2 Pathway

  2003cited by this paper
• Regulatory mechanisms controlling gene expression mediated by the antioxidant response element.

  2003cited by this paper
• Modulation of Gene Expression by Cancer Chemopreventive Dithiolethiones through the Keap1-Nrf2 Pathway IDENTIFICATION OF NOVEL GENE CLUSTERS FOR CELL SURVIVAL*

  2003cited by this paper
• Roles of Nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements.

  2002cited by this paper
• Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment.

  2002cited by this paper
• Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray.

  2002cited by this paper
• Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice.

  2002cited by this paper
• Phosphorylation of Nrf2 at Ser-40 by Protein Kinase C Regulates Antioxidant Response Element-mediated Transcription*

  2002cited by this paper
• Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment.

  2002cited by this paper
• Interaction of heme with nitroxyl or nitric oxide amplifies heme oxygenase-1 induction: involvement of the transcription factor Nrf2.

  2002cited by this paper
• Heme Oxygenase-1: Past, Present, and Future

  2002cited by this paper
• Toxic effect of inhibition of glutathione synthesis on human embryonic kidney cells

  2002cited by this paper
• The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes.

  2001cited by this paper
• Nrf2-dependent activation of the antioxidant responsive element by tert-butylhydroquinone is independent of oxidative stress in IMR-32 human neuroblastoma cells.

  2001cited by this paper
• An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen

  2001cited by this paper
• The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin.

  2000cited by this paper
• Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages*

  2000cited by this paper
• Enhanced expression of pulmonary gamma-glutamylcysteine synthetase heavy subunit in rats exposed to cadmium aerosols.

  2000cited by this paper
• Regulation of γ-glutamylcysteine synthetase subunit gene expression: Insights into transcriptional control of antioxidant defenses

  2000cited by this paper
• Nrf2 is essential for protection against acute pulmonary injury in mice.

  1999cited by this paper
• Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain.

  1999cited by this paper
• Nrf2, a Cap’n’Collar Transcription Factor, Regulates Induction of the Heme Oxygenase-1 Gene*

  1999cited by this paper
• Regulation of γ-Glutamylcysteine Synthetase Subunit Gene Expression by the Transcription Factor Nrf2*

  1999cited by this paper
• Activation of nuclear factor kappa B (NF-kappaB) assayed by laser scanning cytometry (LSC).

  1998cited by this paper
• Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion.

  1997cited by this paper
• Functional antioxidant responsive elements.

  1997cited by this paper
• An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements.

  1997cited by this paper
• Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene.

  1996cited by this paper
• Heme oxygenase-1 gene expression by a glutathione depletor, phorone, mediated through AP-1 activation in rats.

  1996cited by this paper
• Long Exposure to High Glucose Concentration Impairs the Responsive Expression of γ-Glutamylcysteine Synthetase by Interleukin-1β and Tumor Necrosis Factor-α in Mouse Endothelial Cells*

  1996cited by this paper
• Fluorimetric determination of monobromobimane and o-phthalaldehyde adducts of gamma-glutamylcysteine and glutathione: application to assay of gamma-glutamylcysteinyl synthetase activity and glutathione concentration in liver.

  1995cited by this paper
• Cloning and sequencing of the cDNA for the light subunit of human liver gamma-glutamylcysteine synthetase and relative mRNA levels for heavy and light subunits in human normal tissues.

  1995cited by this paper
• Glutathione Depletion Induces Heme Oxygenase‐1 (HSP32) mRNA and Protein in Rat Brain

  1993cited by this paper
• Endogenous glutathione levels modulate both constitutive and UVA radiation/hydrogen peroxide inducible expression of the human heme oxygenase gene.

  1992cited by this paper
• Enhancement of heme oxygenase-1 synthesis by glutathione depletion in Chinese hamster ovary cells.

  1991cited by this paper
• Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: a model for neurotoxicological studies.

  1991cited by this paper
• Possible role of glutathione depletion in the induction of rate-limiting enzymes involved in heme degradation and polyamine biosynthesis in the liver of rats.

  1990cited by this paper
• Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells.

  1989cited by this paper
• ENDOGENOUS GLUTATHIONE PROTECTS HUMAN SKIN FIBROBLASTS AGAINST THE CYTOTOXIC ACTION OF UVB, UVA AND NEAR‐VISIBLE RADIATIONS

  1986cited by this paper
• Mechanisms of selective action of pyrethroid insecticides.

  1983cited by this paper

• The role of the pentose phosphate pathway in the development of metabolic disorders in the testes during rat intoxication with cypermethrin.

  2025cites this paper
• Oxidative stress in animals exposed to cypermethrin: mechanisms of development and possible risks

  2023cites this paper
• A Pacific Oyster-Derived Antioxidant, DHMBA, Protects Renal Tubular HK-2 Cells against Oxidative Stress via Reduction of Mitochondrial ROS Production and Fragmentation

  2023cites this paper
• Pyrethroid based pesticides – chemical and biological aspects

  2021cites this paper
• The Role of Antioxidant on Health and Age-Related Diseases in Aging

  2021cites this paper
• Nano-curcumin versus curcumin in amelioration of deltamethrin-induced hippocampal damage

  2020cites this paper
• Targeting organophosphorus compounds poisoning by novel quinuclidine-3 oximes: development of butyrylcholinesterase-based bioscavengers

  2020cites this paper
• Protective Effect of Bruguiera gymnorrhiza (L.) Lam. Fruit on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice: Role of Keap1/Nrf2 Pathway and Gut Microbiota

  2020cites this paper
• Deltamethrin toxicity: A review of oxidative stress and metabolism

  2019cites this paper
• Evaluation of Nrf2 with Exposure to Nanoparticles.

  2018cites this paper
• Nuclear factor erythroid‐derived 2–related factor 2 activates glutathione S‐transferase expression in the midgut of Spodoptera litura (Lepidoptera: Noctuidae) in response to phytochemicals and insecticides

  2018cites this paper
• Experimental Study of Deltamethrin-Induced Nephrotoxicity in the Rat Model

  2018cites this paper
• Pyrethroid bifenthrin induces oxidative stress, neuroinflammation, and neuronal damage, associated with cognitive and memory impairment in murine hippocampus

  2018cites this paper
• Glutathione as a Marker for Human Disease.

  2018cites this paper
• Efficacy of fresh packed red blood transfusion in organophosphate poisoning

  2017cites this paper
• Molecular mechanisms of pesticides toxicity

  2017cites this paper
• EXPLORING THE ROLE OF MITOCHONDRIAL CHOLESTEROL IN NIEMANN-PICK TYPE C DISEASE

  2016influential citation
• Acute severe organophosphate poisoning in a child who was successfully treated with therapeutic plasma exchange, high‐volume hemodiafiltration, and lipid infusion

  2016cites this paper
• 9-Norbornyl-6-chloropurine (NCP) induces cell death through GSH depletion-associated ER stress and mitochondrial dysfunction.

  2016cites this paper
• Kinetics of pesticide degradation by human fresh frozen plasma (FFP) in vitro.

  2016cites this paper
• TrxR1 as a Potent Regulator of the Nrf2-Keap1 Response System

  2015cites this paper
• Effects of a novel pesticide-particle conjugate on viability and reactive oxygen species generation in neuronal (PC12) cells

  2015cites this paper
• Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication in Neuroprotective Therapy for Parkinson’s Disease

  2015cites this paper