Biphasic activation of apoptosis signal-regulating kinase 1-stress-activated protein kinase 1-c-Jun N-terminal protein kinase pathway is selectively mediated by Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors involving oxidative stress following brain ischemia in rat hippocampus.

Abstract

Stress-activated protein kinase/extracellular signal-regulated kinase-1 (SEK1/MKK4) was examined in a rat model of global brain ischemia. Western blot assay showed that SEK1 activation was biphasic in CA1 but not CA3/dentate gyrus. The second activation peak (3 days after ischemia) was prevented by pretreatment with l-naphthyl acetyl spermine (Naspm), a channel blocker of Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, or N-acetylcysteine (NAC), a free radical scavenger. Concomitantly, the late activation of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal protein kinase (JNK) was also prevented by Naspm or NAC. Moreover, phospho-SEK1 and phospho-JNK co-immunoprecipitated with ASK1 and the bindings peaked at 3 days of reperfusion. Together with previous results, these findings indicate that Ca(2+)-permeable AMPA receptors are important routes to mediate the late activation of ASK1-SEK1-JNK pathway involving oxidative stress in hippocampal CA1 region after ischemia.

• Authors: Quanguang Zhang, Guangyi Zhang, Fanjie Meng, Hui Tian
• Journal: Neuroscience letters (Neurosci Lett) Vol. 337 Issue 1 Pg. 51-5 (Jan 30 2003) ISSN: 0304-3940 [Print] Ireland
• PMID: 12524169 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Calcium Channel Blockers
• Calcium Channels, L-Type
• Receptors, AMPA
• 1-naphthylacetylspermine
• Spermine
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 8
• Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinase 5
• MAP Kinase Kinase Kinases
• Nifedipine
• Calcium
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Animals
• Antioxidants (pharmacology)
• Brain Ischemia (enzymology, metabolism)
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, L-Type (drug effects, metabolism)
• Enzyme Activation
• Hippocampus (metabolism)
• Ion Channel Gating
• JNK Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinase 5
• MAP Kinase Kinase Kinases (metabolism)
• Male
• Mitogen-Activated Protein Kinase 8
• Mitogen-Activated Protein Kinases (metabolism)
• Nifedipine (pharmacology)
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Receptors, AMPA (antagonists & inhibitors, metabolism)
• Spermine (analogs & derivatives, pharmacology)