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.
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.
Guan
Qiu-Hua
QH
Department of Neurobiology & Biophysics, School of Life Science, University of Science & Technology of China, Hefei 230027, PR China.
Pei
Dong-Sheng
DS
Xu
Tian-Le
TL
Zhang
Guang-Yi
GY
D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D000873:Anthracenes; D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; C484585:Hrk protein, rat; D009479:Neuropeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases