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

doi:10.1016/j.neulet.2005.09.075

Neuroscience Letters

Volume 393, Issues 2–3, 30 January 2006, Pages 226-230

https://doi.org/10.1016/j.neulet.2005.09.075 Get rights and content

Abstract

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.

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Acknowledgement

Project supported by the Key Item National Nature Science Foundation (No. 30330190).

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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

Abstract

Section snippets

Acknowledgement

Brain Res.

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

Mol. Brain Res.

J. Biol. Chem.

Cell

Neuroprotection against focal ischemic brain injury by inhibition of c-Jun N-terminal kinase and attenuation of the mitochondrial apoptosis-signaling pathway

J. Cereb. Blood Flow Metab.