Figure 4

Tolvaptan activates the Nrf2/HO-1 antioxidant pathway independently of cAMP signaling. (a) The chemical structure of mozavaptan is similar to that of tolvaptan. The structural difference between tolvaptan and mozavaptan is indicated in red. (b) Both tolvaptan and mozavaptan completely counteracts the effect of dDAVP on AQP2 phosphorylation at S269. Following the pre-incubation of mpkCCD cells using DMSO, 200 μM tolvaptan, or 100 μM mozavaptan for 1 h, 1 nM dDAVP was added for 12 h. The representative blots of three independent experiments are shown. (c) Mozavaptan does not induce HO-1 in mpkCCD cells. (Top panel) mpkCCD cells were treated with 200 μM tolvaptan or 100 μM mozavaptan for 12 h. (Bottom panel) Densitometric analysis of HO-1 is presented. Error bars are mean values ± S.E. from three experiments. Tukey’s test, *P < 0.05. C: control (DMSO), Tol: 200 μM tolvaptan, Mz: 100 μM mozavaptan, Sul: 5 μM sulforaphane. P.C.: positive control, n.s.: not significant.