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.
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Authors | Yan Wang, Huai-Xue Ji, Shu-Hua Xing, Dong-Sheng Pei, Qiu-Hua Guan |
Journal | Life sciences
(Life Sci)
Vol. 80
Issue 22
Pg. 2067-75
(May 08 2007)
ISSN: 0024-3205 [Print] Netherlands |
PMID | 17459422
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthracenes
- Protective Agents
- pyrazolanthrone
- JNK Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Anthracenes
(pharmacology)
- Apoptosis
(drug effects)
- Disease Models, Animal
- JNK Mitogen-Activated Protein Kinases
(antagonists & inhibitors, metabolism)
- Kidney
(enzymology, pathology)
- Kidney Diseases
(drug therapy, enzymology, pathology)
- Necrosis
(metabolism)
- Protective Agents
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Reperfusion Injury
(drug therapy, enzymology, pathology)
- Signal Transduction
(drug effects, physiology)
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