The protein kinase 2 inhibitor tetrabromobenzotriazole protects against renal ischemia reperfusion injury

Abstract

Protein kinase 2 (CK2) activation was reported to enhance reactive oxygen species production and activate the nuclear factor kappa B (NF-kappa B) pathway. Because oxidative stress and inflammation are critical events for tissue destruction during ischemia reperfusion (I/R), we sought to determine whether CK2 was important in the renal response to I/R. Mice underwent 25 min of renal ischemia and were then reperfused. We confirmed an increased expression of CK2 alpha during the reperfusion period, while expression of CK2 beta remained consistent. We administered tetrabromobenzotriazole (TBBt), a selective CK2 alpha inhibitor before inducing I/R injury. Mice subjected to I/R injury showed typical patterns of acute kidney injury; blood urea nitrogen and serum creatinine levels, tubular necrosis and apoptosis, inflammatory cell infiltration and proinflammatory cytokine production, and oxidative stress were markedly increased when compared to sham mice. However, pretreatment with TBBt abolished these changes and improved renal function and architecture. Similar renoprotective effects of CK2 alpha inhibition were observed for emodin. Renoprotective effects of CK2 alpha inhibition were associated with suppression of NF-kappa B and mitogen activated protein kinase (MAPK) pathways. Taken together, these results suggest that CK2 alpha mediates proapoptotic and proinflammatory signaling, thus the CK2 alpha inhibitor may be used to prevent renal I/R injuries observed in clinical settings.