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 gss expression in mouse fibroblasts.
Nrf1 is a member of the CNC-basic leucine zipper (CNC-bZIP) family of transcription 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 promoters of genes involved in detoxification and antioxidant response raises the possibility that Nrf1 plays a role in mediating the antioxidant response element response. In this study, we exploited the availability of cells from Nrf1 knockout mice to study the role of Nrf1 transcription factor in the regulation of antioxidant gene expression and in cellular antioxidant response. Fibroblast cells derived from Nrf1 null embryos showed lower levels of glutathione and enhanced sensitivity to the toxic effects of oxidant compounds. Our results indicate that Nrf1 plays a role in the regulation of genes involved in glutathione synthesis and suggest a basis for a correspondingly low GSH concentration and reduced stress response.
Kwong
M
M
Department of Laboratory Medicine, University of California, San Francisco, California 94143-0793, USA.
Kan
Y W
YW
Chan
J Y
JY
D000818:Animals; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism; D005609:Free Radicals; D015971:Gene Expression Regulation, Enzymologic; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D005978:Glutathione / Q000032:analysis; D005981:Glutathione Synthase / Q000235:genetics*; D016350:Leucine Zippers; D051379:Mice; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015534:Trans-Activators / Q000502:physiology*
D004268:DNA-Binding Proteins; D005609:Free Radicals; C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D015534:Trans-Activators; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione