Antioxidant NAC and AMPA/KA receptor antagonist DNQX inhibited JNK3 activation following global ischemia in rat hippocampus.

Abstract

c-Jun N-terminal kinase-3 (JNK3), the only neural-specific isoform, may play an important role in excitotoxicity and neuronal injury. To analyze the variation of JNK3 activation, levels of phospho-JNK3 were measured at various time points of ischemia and selected time points of reperfusion, respectively. Our study illustrated that JNK3 was rapidly activated and translocated from cytosol to nucleus during ischemia. During reperfusion, two peaks of JNK3 activation occurred at 30 min and 3 days, respectively. To further define the mechanism of JNK3 activation, antioxidant N-acetylcysteine (NAC), alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA) receptor antagonist 6,7-dinitro-quinoxaline-2,3(1H,4H)-dione (DNQX), N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist nifedipine were given to the rats 20 min prior to ischemia. The results showed that NAC obviously inhibited JNK3 activation during the early reperfusion, whereas DNQX preferably attenuated JNK3 activation during the latter reperfusion. Ketamine and nifedipine had no significant effects on JNK3 activation during reperfusion. Consequently, reactive oxygen species (ROS) and AMPA/KA receptor were closely associated with JNK3 activation following global ischemia.

• Authors: Hui Tian, Guangyi Zhang, Hongchun Li, Quanguang Zhang
• Journal: Neuroscience research (Neurosci Res) Vol. 46 Issue 2 Pg. 191-7 (Jun 2003) ISSN: 0168-0102 [Print] Ireland
• PMID: 12767482 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Excitatory Amino Acid Antagonists
• Free Radical Scavengers
• Quinoxalines
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• FG 9041
• Ketamine
• Mitogen-Activated Protein Kinase 10
• Protein-Tyrosine Kinases
• Mitogen-Activated Protein Kinases
• Nifedipine
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Brain Ischemia (enzymology)
• Calcium Channel Blockers (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Free Radical Scavengers (pharmacology)
• Immunoblotting
• Ketamine (pharmacology)
• Male
• Mitogen-Activated Protein Kinase 10
• Mitogen-Activated Protein Kinases (drug effects, metabolism)
• Nifedipine (pharmacology)
• Protein Transport
• Protein-Tyrosine Kinases (drug effects, metabolism)
• Quinoxalines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, AMPA (antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Time Factors