Figure 7.
Genetic deficiency of Nox4, but not of Nox1, and pharmacologic Nox inhibition attenuate increased renal superoxide and ROS formation in diabetic ApoE−/− mice. Superoxide production in renal cortex (A, C, and E) and ROS production in cytosolic and mitochondrial fractions of the renal cortex (B, D, and F) in control and diabetic Nox4+/+ApoE−/− and Nox4−/−ApoE−/− mice (A and B), control and diabetic Nox1+/yApoE−/− and Nox1−/yApoE−/− mice after 20 weeks (C and D), or control and diabetic ApoE−/− mice with and without treatment with GKT137831 for 20 weeks (E and F) (n=5–6 per group). Superoxide data (A, C, and E) are shown as the ratio of 2HE (nanomoles) to DHE (micromoles). With respect to ROS measurements, results were expressed relative to control Nox4+/+ApoE−/− mice (B), control Nox1+/yApoE−/− mice (D), or control (untreated) ApoE−/− mice (F), which was arbitrarily assigned a value of 100. Data are the mean±SEM. *P≤0.05 versus respective control Nox4+/+ApoE−/− or control Nox1+/yApoE−/− mice or control ApoE−/− mice; #P<0.05 versus diabetic Nox4+/+ApoE−/− or diabetic ApoE−/− mice. 2HE, 2 hydroethidium; Cont, control; Diab, diabetes; DHE, dihydroethidium; GKT, GKT137831; RLU, relative light unit.