Brain ischemia/reperfusion-induced expression of DP5 and its interaction with Bcl-2, thus freeing Bax from Bcl-2/Bax dimmers are mediated by c-Jun N-terminal kinase (JNK) pathway

• Published in: Neuroscience letters Vol. 393; no. 2; pp. 226 - 230
• Main Authors: Guan, Qiu-Hua, Pei, Dong-Sheng, Xu, Tian-Le, Zhang, Guang-Yi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 30.01.2006; Elsevier
• Subjects: Analysis of Variance; Animals; Anthracenes - pharmacology; Apoptosis Regulatory Proteins - metabolism; Bcl-2; bcl-2-Associated X Protein - metabolism; Bcl-2/Bax dimers; Biological and medical sciences; Blotting, Western - methods; Brain Ischemia - metabolism; c-Jun N-terminal kinase (JNK); Cerebral ischemia; Disease Models, Animal; DP5; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Hippocampus - metabolism; Immunoprecipitation - methods; JNK Mitogen-Activated Protein Kinases - metabolism; Male; Medical sciences; Neurology; Neuropeptides - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion; Time Factors; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Bcl-2; DP5; c-Jun N-terminal kinase (JNK); Cerebral ischemia; Bcl-2/Bax dimers; c-Jun N-terminal kinase; Enzyme; Central nervous system; Mitogen-activated protein kinase; Cardiovascular disease; Encephalon; Reperfusion; Ischemia
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2005.09.075

Our previous studies and those of others have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. But the downstream mechanism that accounts for the proapoptotic actions of JNK during cerebral ischemia/reperfusion still remains to be investigated in detail. DP5, one of the mammalian BH3-only proteins, was cloned as a neuronal apoptosis-inducing gene. In this study, we examined the changes of protein level of DP5 and its interaction with Bcl-2 family members in a rat model of global ischemia and reperfusion by immunoprecipitation and immunoblotting; furthermore, we investigated the effect of activated JNK on DP5-signaling pathway. We show here that DP5 was induced and interacted with Bcl-2 but not Bax in hippocampal CA1 6 h to 3 days after ischemia, while the interaction of Bcl-2 with Bax decreased. Systemic administration of SP600125, a small molecule JNK-specific inhibitor, diminished the induction of DP5 and its interaction with Bcl-2 after 2 days of ischemia. At the same time, SP600125 increased the interaction of Bax with Bcl-2 after 2 days of reperfusion. Thus, these results indicate that brain ischemia/reperfusion-induced activation of DP5 signaling pathway is mediated by JNK in postischemic rat hippocampal CA1.