K252a suppresses neuronal cells apoptosis through inhibiting the translocation of Bax to mitochondria induced by the MLK3/JNK signaling after transient global brain ischemia in rat hippocampal CA1 subregion.

Abstract

It is demonstrated that the c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. Our previous studies have suggested that K252a can obviously inhibit JNK activation induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. Here, we further discussed the potential mechanism of ischemic brain injury induced by the activation of JNK after 15?min of transient global cerebral ischemia. As a result, through inhibiting phosphorylation of Bcl-2 (a cytosolic target of JNK) and 14-3-3 protein (a cytoplasmic anchor of Bax) induced by the activation of JNK, K252a decreased the release of Bax from Bcl-2/Bax and 14-3-3/Bax dimers, further attenuating the translocation of Bax from cytosol to mitochondria and the release of cytochrome c induced by ischemia/reperfusion, which related to mitochondria-mediated apoptosis. Importantly, pre-infusion of K2525a 20?min before ischemia showed neuroprotective effect against neuronal cells apoptosis. These findings imply that K252a induced neuroprotection against ischemia/reperfusion in rat hippocampal CA1 subregion via inhibiting the mitochondrial apoptosis pathway induced by JNK activation.

• Authors: Qing Wang, Xiao-Hui Yin, Yong Liu, Guang-Yi Zhang
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 31 Issue 4 Pg. 307-13 (Aug 2011) ISSN: 1532-4281 [Electronic] England
• PMID: 21726169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 14-3-3 Proteins
• Carbazoles
• Enzyme Inhibitors
• Indole Alkaloids
• Neuroprotective Agents
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Cytochromes c
• staurosporine aglycone
• JNK Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinases
• mitogen-activated protein kinase kinase kinase 11

Topics

• 14-3-3 Proteins (metabolism)
• Animals
• Apoptosis (drug effects)
• Brain Ischemia (metabolism, pathology)
• CA1 Region, Hippocampal (cytology, pathology, physiopathology)
• Carbazoles (pharmacology)
• Cytochromes c (metabolism)
• Enzyme Inhibitors (pharmacology)
• Indole Alkaloids (pharmacology)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• MAP Kinase Kinase Kinases (metabolism)
• Male
• Mitochondria (metabolism)
• Neurons (cytology, drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• bcl-2-Associated X Protein (metabolism)