Original Article Diabetes-Induced Activation of Canonical and Noncanonical Nuclear Factor-B Pathways in Renal Cortex

Evidence of diabetes-induced nuclear factor-B (NF-B) activation has been provided with DNA binding assays or nuclear localization with immunohistochemistry, but few studies have explored mechanisms involved. We examined effects of diabetes on proteins comprising NF-B canonical and noncanonical activation pathways in the renal cortex of diabetic mice. Plasma concentrations of NF-B–regu-lated cytokines were increased after 1 month of hypergly-cemia, but most returned to control levels or lower by 3 months, when the same cytokines were increased signifi-cantly in renal cortex. Cytosolic content of NF-B canoni-cal pathway proteins did not differ between experimental groups after 3 months of diabetes, while NF-B noncanoni-cal pathway proteins were affected, including increased phosphorylation of inhibitor of B kinase- and severa