A conserved role for the 20S proteasome and Nrf2 transcription factor in oxidative-stress adaptation in mammals, C. elegans and D. melanogaster

Abstract

Summary In mammalian cells H2O2 induced adaptation to oxidative stress is strongly dependent on an Nrf2 mediated increase in 20S proteasome. Here we report that both Caenorhabditis elegans nematode worms and Drosophila melanogaster fruit-flies are also capable of adapting to oxidative stress with H2O2 pretreatment. As in mammalian cells, this adaptive response in worms and flies involved an increase in proteolytic activity and increased expression of 20S proteasome, but not of 26S proteasome. It was also found that the increase in 20S proteasome expression in both worms and flies, as in mammalian cells, is important for the adaptive response, and that it is mediated by the SKN-1 and CNC-C orthologs of the mammalian Nrf2 transcription factor, respectively. These studies demonstrate that stress mechanisms operative in cell culture also apply in disparate intact organisms across a wide range of biological diversity.