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Reactive oxygen species mediate ERK activation through different Raf-1-dependent signaling pathways following cerebral ischemia

Authors
Journal
Neuroscience Letters
0304-3940
Publisher
Elsevier
Publication Date
Volume
432
Issue
2
Identifiers
DOI: 10.1016/j.neulet.2007.11.073
Keywords
  • Cerebral Ischemia
  • Ros
  • Phosphorylation
  • Erk
  • Raf-1

Abstract

Abstract Production of reactive oxygen species (ROS) results in up-regulation of the extracellular signal-regulated kinase (ERK) cascade in response to numerous stimuli. Cerebral ischemia induces calcium-dependent kinase activation followed by ROS production. Here, we examined how ROS mediates the activation of ERK following cerebral ischemia in the rat hippocampus. We found that alpha-tocopherol, a free radical scavenger, attenuated the initial, robust activation of ERK by inhibiting Raf-1 dephosphorylation at Ser259. Alpha-tocopherol also down-regulated the second and mild activation of ERK through inhibition of Src-dependent phosphorylation of Raf-1 at Tyr340/341. Our results suggest that ROS production mediates the biphasic activation of ERK through different signaling cascades following post-ischemic reperfusion. Mediation of these signaling pathways involves changes in Raf-1 phosphorylation at different sites.

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