Abstract 75: Nrf2 Mediates the Antioxidant Effect of D2r Via Dj-1 in the Kidney [Oral Session IX: Concurrent B Oxidative Stress]

Renal dopamine D2 receptor (D2R) dysfunction is associated with increased oxidative stress and high blood pressure. We have reported that DJ-1 is regulated by D2R in the kidney. Nrf2 is a transcription factor that regulates the expression of several antioxidant genes. We hypothesize that Nrf2 is involved in the DJ-1-mediated regulation of reactive oxygen species (ROS) production in the kidney. DJ-1 and Nrf2 co-inmunoprecipitate in mouse kidney. Selective renal silencing of D2R in mice by the renal subcapsular infusion of D2R siRNA (~50%) decreases Nrf2 expression (63.4%±3.4, n=7, P<0.05), and silencing of D2R expression in mouse proximal tubule cells (mRPTCs) decrease Nrf2 promoter activity (53±2%, n=5, P<0.05). Silencing DJ-1 expression in mRPTCs, via siRNA, decreases the expression of DJ-1 (75±4.5%, n=4, P<0.05), Nrf2 (63.2±6%, n=3, P<0.05), NQO1 (71±1%, n=3, P<0.05), and GST Yc-2 (42±1%, n=4, P<0.05) and Nrf2 promoter activity (58±1%, n=5, P<0.05). Selective renal silencing of DJ-1 in mice by renal subcapsular infusion of DJ-1 siRNA decreases expression of DJ-1 (31±2.6%, n=3, P<0.05), Nrf2 (57±7.9%,n=3, P<0.05), NQO1 (46±9.3%, n=3, P<0.05) and GST Yc2 (28±2.2%, n=3, P<0.05) and increases blood pressure (BP). DJ-1-/- mice also have increased systolic BP (30.7±1%, P<0.01, n=5 under anesthesia) and renal expression of nitro-tyrosine (76.8±13.5%, P<...
Source: Hypertension - Category: Cardiology Authors: Tags: Oral Session IX: Concurrent B Oxidative Stress Source Type: research