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

Neurosci Lett. 2003 Jan 30;337(1):51-5. doi: 10.1016/s0304-3940(02)01295-8.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Brain Ischemia / enzymology
  • Brain Ischemia / metabolism*
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / 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
  • Receptors, AMPA / metabolism*
  • Spermine / analogs & derivatives*
  • Spermine / pharmacology

Substances

  • 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