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

Huang Yuan Li, Yu Fang Zhong, Si Ying Wu, Nian Shi
Chemical Research in Toxicology 2007, 20 (9): 1242-51
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.

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