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Product Reference
SP600125, a selective JNK inhibitor, protects ischemic renal injury via suppressing the extrinsic pathways of apoptosis.
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| Author |
Yan Wang, Huai-Xue Ji, Shu-Hua Xing, Dong-Sheng Pei, Qiu-Hua Guan |
| Citation Information |
Life sciences, 80:2067-75 (2007) |
| Keywords |
Animals, Anthracenes, Apoptosis, Disease Models, Animal, JNK Mitogen-Activated Protein Kinases, Kidney, Kidney Diseases, Necrosis, Protective Agents, Rats, Rats, Sprague-Dawley, Reperfusion Injury, Signal Transduction |
| Related Products |
S7100 |
| Pub Med ID |
17459422 |
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Abstract
Accumulating evidence suggests that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in renal ischemia/reperfusion injury. However, the downstream mechanism that accounts for the proapoptotic actions of JNK during renal ischemia/reperfusion has not been elucidated. We report that SP600125, a potent, cell-permeable, selective, and reversible inhibitor of c-Jun N-terminal kinase (JNK), potently decreased renal epithelial tubular cell apoptosis induced by renal ischemia/reperfusion via suppression of the extrinsic pathway. This corresponds to the decrease in JNK phosphorylation at 20 min and c-Jun phosphorylation (Ser63/73) at 3 h after renal ischemia. Additionally, SP600125 attenuated the increased expression of FasL induced by ischemia/reperfusion at 3 h. The administration of SP600125 prior to ischemia was also protective. Thus, our findings imply that SP600125 can inhibit the activation of the JNK-c-Jun-FasL pathway and protect renal tubular epithelial cells against ischemia/reperfusion-induced apoptosis. Taken together, these results indicate that targeting the JNK pathway provides a promising therapeutic approach for renal ischemia/reperfusion injury.
