Additive or synergistic activation of Keap1/Nrf2 pathway and enhancement of toxicity by combined exposure to environmental electrophiles

Abstract

Environmental electrophiles modify thiol groups of sensor proteins, leading to activation of redox signaling such as the Keap1/Nrf2 pathway. While activation of Nrf2 by single exposure has been established well, effect of combination of other electrophiles on the activation has not been evaluated. Here, we examined whether or not atmospheric electrophiles such as 1,2- naphthoquinone and 1,4-naphthoquinone could enhance a phytochemical (E)-2-hexenal-mediated Nrf2 activation in HepG2 cells.