The implication of p66shc in oxidative stress induced by deltamethrin

Abstract

Deltamethrin (DLT) is effective against a broad spectrum of insects. Exposure to DLT has been demonstrated to cause oxidative stress. However, the mechanism of oxidative stress induced by DLT is little known. Groups of rats were gavaged with DLT once daily for 7 days at six dosages: 0, 2, 5, 10, 20, 40 mg/kg. The intensity of neurotoxicity and liver dysfunction caused by DLT were significantly increased in a dose-dependent manner. We found that DLT caused the increase of cytosolic superoxide in tissues. Western blot analysis showed that both the expression of p66shc and Ser36 phosphorylated p66shc, which were involved in ROS generation, were increased in tissues treated with DLT. Further investigation showed that DLT treatment resulted in the increase of intracellular ROS accompanied with elevated p66shc expression in different cell lines. And treatment of cells with DLT induced p66shc phosphorylation at Ser36 and the translocation of p66shc from cytoplasm to mitochondria. Moreover, the overexpression of wildtype p66shc caused the increase of DLT-mediated ROS level in SH-SY5Y cells, but cells overexpressing p66shcSer36Ala mutant plasmid had the opposite effect. And p66shc suppression by siRNA blunted DLT-mediated ROS generation. Taken together, our findings indicated p66shc mediated DLT-induced oxidative stress, which may be partly responsible for toxic effects.