casein-kinase-ii and Kidney-Diseases

Protein kinase 2 (CK2) activation was reported to enhance reactive oxygen species production and activate the nuclear factor κB (NF-κB) 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 CK2α during the reperfusion period, while expression of CK2β remained consistent. We administered tetrabromobenzotriazole (TBBt), a selective CK2α 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 CK2α inhibition were observed for emodin. Renoprotective effects of CK2α inhibition were associated with suppression of NF-κB and mitogen activated protein kinase (MAPK) pathways. Taken together, these results suggest that CK2α mediates proapoptotic and proinflammatory signaling, thus the CK2α inhibitor may be used to prevent renal I/R injuries observed in clinical settings.

Topics: Animals; Apoptosis; Casein Kinase II; Extracellular Signal-Regulated MAP Kinases; Gene Expression; Inflammation Mediators; Kidney Diseases; Male; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors; Reperfusion Injury; Signal Transduction

Protein kinase casein kinase II (PKCK2) has multiple, overlapping roles in induction of apoptosis. Apoptosis can be a common pathway of renal injury caused by a nephrotoxic drug or an injury. We evaluated the role of PKCK2 in cyclosporine (CsA)-induced nephropathy in rats by inhibiting PKCK2 with emodin.. Male Sprague-Dawley rats fed a low-sodium diet were divided into four treatment groups: control (0.9% saline injection), CsA (15 mg/kg/d subcutaneously), CsA + emodin (CsA plus emodin 20 mg/kg/d subcutaneously), and emodin only. The expression levels of apoptosis-associated factors and of PKCK2 were examined by Western blot analysis.. Overexpression of PKCK2 noted with CsA treatment was prevented by emodin, a low-molecular-weight PKCK2 inhibitor, which dampend drug-induced up-regulation phosphorylated p53 and activation of caspases 3, 7, and 8. In addition, emodin prevented increased Bax/Bcl-2 ratio induced by CsA. Emodin prevented up-regulation of PKCK2 by CsA treatment, suggesting that its apoptotic-preventing activity was mediated via PKCK2.. Our findings indicated that PKCK2 may play a role in apoptotic injury associated with CsA-induced nephropathy in rats.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Casein Kinase II; Caspase 3; Caspase 7; Caspase 8; Cyclosporine; Diet, Sodium-Restricted; Disease Models, Animal; Emodin; Immunohistochemistry; Kidney; Kidney Diseases; Male; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Tumor Suppressor Protein p53