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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / pharmacology
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Animals
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Antioxidants / pharmacology
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Brain Ischemia / enzymology
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Brain Ischemia / metabolism*
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Calcium / metabolism*
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Calcium Channel Blockers / pharmacology
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Calcium Channels, L-Type / drug effects
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Calcium Channels, L-Type / metabolism
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Enzyme Activation
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Hippocampus / metabolism*
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Ion Channel Gating
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 5
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MAP Kinase Kinase Kinases / metabolism*
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Male
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases / metabolism*
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Nifedipine / pharmacology
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Oxidative Stress*
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Rats
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Rats, Sprague-Dawley
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Receptors, AMPA / antagonists & inhibitors
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Receptors, AMPA / metabolism*
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Spermine / analogs & derivatives*
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Spermine / pharmacology
Substances
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Antioxidants
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Calcium Channel Blockers
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Calcium Channels, L-Type
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Receptors, AMPA
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1-naphthylacetylspermine
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Spermine
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 8
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase Kinase 5
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MAP Kinase Kinase Kinases
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Nifedipine
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Calcium
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Acetylcysteine