title: 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.
authors.affiliation: Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, 92 Chilam dong, Jinju 660-751, Republic of Korea.
authors.forename: Min Kyu
authors.initials: MK
authors.lastname: Park
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Hyun Suk
authors.initials: HS
authors.lastname: Lee
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000201:enzymology; D020520:Brain Infarction / Q000201:enzymology*; D002536:Cerebral Arteries; D002867:Chromones / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D019194:Ischemic Preconditioning; D007783:Lactones / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013450:Sulfones / Q000494:pharmacology
chemical_list: D002867:Chromones; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D015232:Dinoprostone; D006419:Heme Oxygenase (Decyclizing); D007783:Lactones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D013450:Sulfones; C116926:rofecoxib; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C491523:Hmox1 protein, rat; C489691:Ptgs2 protein, rat