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 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.

• Authors: Sun-O Ka, Hong Pil Hwang, Jong-Hwa Jang, In Hyuk Bang, Ui-Jin Bae, Hee Chul Yu, Baik Hwan Cho, Byung-Hyun Park
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 14816 (Oct 01 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26423352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• NF-kappa B
• Protein Kinase Inhibitors
• Casein Kinase II
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Casein Kinase II (antagonists & inhibitors, genetics, metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression
• Inflammation Mediators (metabolism)
• Kidney Diseases (drug therapy, genetics, metabolism, pathology)
• Male
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Reperfusion Injury (drug therapy, genetics, metabolism, pathology)
• Signal Transduction (drug effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)