Project description:Genetic disruption of Gsr in mouse elicits only subtle changes in the liver transcriptome. Transcriptome analysis of Gsr-null livers was performed to further our understanding of pathways that may compensate for loss of Gsr, one of the two NADPH-dependent cytosolic disulfide reductases.
Project description: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.
Project description:Gsr is an antioxidant enzyme responsible for maintaining the supply of reduced glutathiones which reduce reactive oxigen species and maintain cellular redox balance. However, the the role for Gsr in the developemnt of oxidative lung injury is not well characterized. We used microarray analysis to identify Gsr-dependent genes and pathways in embyronic, neonate, and adult lungs. We also determined Gsr-dependent lung transcriptomics in mouse neonates and adults which were neonatally exposed to hyperoxia (O2) or air.