Project description:Autophagy deficiency caused by conditional knockout of Atg7 results in severe hepatitis accompanied by abundant accumulation of p62. p62 stablizes Nrf2 by disrupting the association between Keap1 and Nrf2. To understand the pathogenesis of hepatitis under the autophagy deficiency, we examined gene expression profiles of livers from Atg7-null, Nrf2-null and Atg7-Nrf2 double mutant mice. Eight week old Atg7F/F:Mx1-Cre mice and Atg7F/F:Mx1-Cre:Nrf2-/- together with control mice were injected with pIpC. At 4 weeks after pIpC injection, total RNAs were purified from each mouse liver.
Project description:Autophagy deficiency caused by conditional knockout of Atg7 results in severe hepatitis accompanied by abundant accumulation of p62. p62 stablizes Nrf2 by disrupting the association between Keap1 and Nrf2. To understand the pathogenesis of hepatitis under the autophagy deficiency, we examined gene expression profiles of livers from Atg7-null, Nrf2-null and Atg7-Nrf2 double mutant mice.
Project description:Expression array analysis of mice livers with conditional deletion of autophagy related protein 7 (Atg7). Whole RNA from mice livers of 2 month old control (Atg7 FF), Olig1-CRE:Atg7 FF (conditional deletion in hepatocytes) and Alb-CRE:Atg7 FF (conditional deletion in hepatocytes/cholangiocytes) were analyzed. The results provide insight into the gene expression profile and role of autophagy in hepatocytes or hepatocytes/cholangiocytes in hepatic growth regulation and hepatocarcinogenesis.
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:Oltipraz is an activator of Nrf2 but is also an activator of other pathways including those mediated by constitutive activated receptor (CAR). To identify genes regulated by oltipraz that were Nrf2-dependent, we compared gene expression after exposure in wild-type and Nrf2-null mice. Wild-type or Nrf2-null mice were treated each day for 4 days with 75 mg/kg/day/day oltipraz in corn oil or corn oil alone. There were 4 biological replicates used for each of the 4 genotype-treatment groups. Gene expression in the livers of the mice was evaluated using Affymetrix mouse exon arrays (MoEx-1_0-st-v1).