Abstract: FR-PO360
Direct Inhibitory Effect of Sodium on Nrf2 Expression in Collecting Duct Cells
Session Information
- CKD: Mechanisms - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Author
- Liu, Mi, Southern Medical University Shunde Hospital, Foshan, Guangdong, China
Background
High salt is associated with the progression of CKD. High salt also contributes to oxidative stress in renal tissue and cells. However it remains unclear if high salt is involved in the pathogenesis of CKD through the regulation of oxidative stress. Nuclear factor E2-related factor 2 (Nrf2) is a transcriptional factor which regulates the expression of downstream antioxidant and detoxifying genes. The study was aimed at clarifying whether high salt will affect Nrf2 expression and Nrf2-dependent pathway.
Methods
Mice was treated with acute salt loading. Nrf2 expression in the kidney were detected by western blotting and immunostaining. mpkCCD cells were cultured in high osmolarity medium by adding NaCl. We measured the expression of Nrf2 and Nrf2-dependent genes via western blotting and qRT-PCR. Pretreatment with NAC, spironolactone or NS-398 in mpkCCD cells were performed and Nrf2 mRNA expression were monitored.
Results
Nrf2 protein levels in the kidney were markedly downregulated after acute salt loading. Nrf2 was remarkably downregulated in mpkCCD cells after NaCl treatment. Sodium gluconate had a similar effect on Nrf2 expression as NaCl, whereas neither Choline-Cl nor mannitol changed Nrf2 protein level. The mRNA levels of Nrf2-dependent genes were downregulated by NaCl mainly dependent on the effect of Na+. The downregulation of Nrf2 was not affected by NAC, spironolactone or NS-398.
Conclusion
Sodium has a direct inhibitory effect on the expression of Nrf2 and Nrf2-dependent genes.
Figure 1. Nrf2 protein expression in kidneys after acute high salt loading.
Nrf2 expression in mpkCCD cells after NaCl, Na-Glu,Choline-Cl and mannitol treatment