Nrf2 mediates induction of cytoprotective genes in response to Cd exposure

摘要

Cadmium is known to elicit a wide range of pathological disorders in exposed cells through different mechanisms which include induction of oxidative stress and alteration in signal transduction pathways (Skalhegg and Tasken, 2000). In order to cope with environmental insults, cells have mechanisms that trigger adaptive response that help to eliminate or reduce the effect of these stresses. Some of these responses are mediated by the Nrf2-Keapl-ARE pathway that regulates the expressions of cytoprotective enzymes (Itoh et al., 1997). In this study, we have evaluated the role of Nrf2 in mediating the adaptive response of three human cell lines to Cd exposure: human hepatoma (HepG2) cells, human astrocy-toma (1321N1) cells and human embryonic kidney (HEK 293) cells. We found that exposure to 5, 10 and 50muM Cd for 24 h significantly induced the protein expressions of NAD (P) H: quinone oxidoreductase (NQO1), heme oxygenase 1 (HO1) and gamma-glutamyl cysteine synthase (gamma-GCSc) in all the three cell lines (Fig. 1). Examinations of the cytosolic and nuclear fractions of these cell lines reveal that Nrf2 protein levels increases in the nucleus and decreases in the cytoplasm. However, increases in keap1 levels were also observed in the cytosol as Cd concentrations increases.