Elevated Nrf2 response in TrxR1/Gsr-null livers

Liver-specific depletion of both of the cytosolic NADPH-dependent disulfide reductases, TrxR1 and Gsr, was shown to result in increased activation of Nrf2 as compared to elimination of either of these enzymes alone. Activation of transcription factor Nrf2 and its downstream cytoprotective target genes by oxidative and electrophilic insults can protect cells from potentially carcinogenic damage. However, many cancers have an activated Nrf2 response, which can protect cancer cells from oxidative stress radiation. Gene expression profiles in TrxR1/Gsr-null livers provide a basis for understanding the complex responses to chronically elevated oxidative stress and damage. Livers were harvested from female wild-type and TrxR1/Gsr-null 4-week-old mice (n = 4, each genotype) between 10:00 a.m. and 11:30 a.m. Liver RNA was purified and processed for microarray analysis.