The CNC basic leucine zipper factor, Nrf1, is essential for cell survival in response to oxidative stress-inducing agents - Role for Nrf1 in gamma-gcs(L) and g(ss) expression in mouse fibroblasts

Nrf1 is a member of the CNC-basic leucine zipper (CNC-bZIP) family of trans cription factors. CNC bZIP factors, together with small Maf proteins, bind as heterodimers to the NF-E2/AP-1 element. Similarity between the NF-E2/AP- 1 element and the antioxidant response element identified in a number of pr omoters of genes involved in detoxification and antioxidant response raises the possibility that Nrf1 plays a role in mediating the antioxidant respon se element response. In this study, we exploited the availability of cells from Nrf1 knockout mice to study the role of Nrf1 transcription factor in t he regulation of antioxidant gene expression and in cellular antioxidant re sponse. Fibroblast cells derived from Nrf1 null embryos showed lower levels of glutathione and enhanced sensitivity to the toxic effects of oxidant co mpounds. Our results indicate that Nrf1 plays a role in the regulation of g enes involved in glutathione synthesis and suggest a basis for a correspond ingly low GSH concentration and reduced stress response.