The obligatory role of COX-2 expression for induction of HO-1 in ischemic preconditioned rat brain.

Abstract

The molecular mechanisms of preconditioning-induced ischemic tolerance (PCIT) have yet to be elucidated. We investigated whether minimal expression levels of COX-2 induced by preconditioning trigger HO-1, thereby inducing the synthesis of cytoprotective proteins. We show that both COX-2 and HO-1 are induced in rat brains subjected to preconditioning by middle cerebral artery (MCA) occlusion for 10 min followed by different amounts of reperfusion time (1-24 h). Although preconditioning significantly reduced the brain infarct size against severe ischemia (24 h MCA occlusion), pretreatment with the COX-2-selective inhibitor rofecoxib increased infarct size and abolished PCIT-induced COX-2 and HO-1 expression in vivo. We also found that PGE(2) increased the phosphorylation of Akt, which was significantly inhibited by the PI3 kinase inhibitor LY294002. Taken together, we conclude that the kinetic changes in COX-2 induction during the reperfusion period following preconditioning may be important for ischemic tolerance.

DOI: 10.1016/j.bbrc.2008.10.149

Cite this paper

@article{Park2008TheOR, title={The obligatory role of COX-2 expression for induction of HO-1 in ischemic preconditioned rat brain.}, author={Min Kyu Park and Young Jin Kang and Hyun Suk Lee and Hye Jung Kim and Han Geuk Seo and Jae Heun Lee and Ki Churl Chang}, journal={Biochemical and biophysical research communications}, year={2008}, volume={377 4}, pages={1191-4} }