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NF-E2 related factor 2 activation and heme oxygenase-1 induction by tert-butylhydroquinone protect against deltamethrin-mediated oxidative stress in PC12 cells

Chem Res Toxicol. 2007 Sep;20(9):1242-51. doi: 10.1021/tx700076q. Epub 2007 Aug 4.

Abstract

Recent findings suggest that oxidative stress caused by pyrethroid pesticides could be closely involved in the neurotoxicity. tert-Butylhydroquinone ( tBHQ) is a known inducer of Nrf2-mediated transcription, and treatment of cells with tBHQ can confer protection against H 2O 2 and 6-hydroxydopamine (6-OHDA). In this study, we investigated the neuroprotective effect of tBHQ against deltamethrin (DM)-induced oxidative stress using rat PC12 adrenal pheochromocytoma cells. The pretreatment of PC12 cells with tBHQ significantly reduced DM-induced generation of reactive oxygen species (ROS) and increased intracellular ionized calcium ([Ca (2+)] i). We also observed that DM or tBHQ induced the expression of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), a Nrf2-regulated gene. In addition, the Nrf2 antioxidant responsive element (ARE) pathways activated by tBHQ caused a partial inhibition of the DM-induced Nrf2 and HO-1 expression. Altogether, our data clearly indicate that an activation of Nrf2/ARE pathways in PC12 cells by tBHQ treatment protects cells from DM-induced oxidative stress and regulates DM- mediated adaptive responses in PC12 cells via translocation of Nrf2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Calcium / analysis
  • Heme Oxygenase-1 / metabolism*
  • Hydroquinones / pharmacology*
  • Immunohistochemistry
  • Insecticides / toxicity
  • NF-E2-Related Factor 2 / metabolism*
  • Nitriles / toxicity*
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Oxidopamine / toxicity
  • PC12 Cells
  • Pyrethrins / toxicity*
  • Rats
  • Reactive Oxygen Species / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Antioxidants
  • Hydroquinones
  • Insecticides
  • NF-E2-Related Factor 2
  • Nitriles
  • Pyrethrins
  • Reactive Oxygen Species
  • decamethrin
  • Oxidopamine
  • 2-tert-butylhydroquinone
  • Heme Oxygenase-1
  • Calcium