Microsomal prostaglandin E synthase-1 is a critical factor of stroke-reperfusion injury
| Autor: | Tetsuya Fukada, Yuri Ikeda-Matsuo, Yasuharu Sasaki, Satoshi Uematsu, Azusa Ota, Shizuo Akira |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Ischemia Apoptosis Biology Dinoprostone Rats Sprague-Dawley Lesion Mice Microsomes Internal medicine Edema medicine Animals Humans Prostaglandin-E Synthases Mice Knockout Multidisciplinary Behavior Animal Microglia Biological Sciences medicine.disease Rats Intramolecular Oxidoreductases Isoenzymes Mice Inbred C57BL Stroke Endocrinology medicine.anatomical_structure Cerebral cortex Reperfusion Injury Immunology lipids (amino acids peptides and proteins) medicine.symptom Reperfusion injury Prostaglandin E |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:11790-11795 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Although augmented prostaglandin E 2 (PGE 2 ) synthesis and accumulation have been demonstrated in the lesion sites of rodent transient focal ischemia models, the role of PGE 2 in neuronal survival has been controversial, showing both protective and toxic effects. Here we demonstrate the induction of microsomal PGE synthase 1 (mPGES-1), an inducible terminal enzyme for PGE 2 synthesis, in neurons, microglia, and endothelial cells in the cerebral cortex after transient focal ischemia. In mPGES-1 knockout (KO) mice, in which the postischemic PGE 2 production in the cortex was completely absent, the infarction, edema, apoptotic cell death, and caspase-3 activation in the cortex after ischemia were all reduced compared with those in wild-type (WT) mice. Furthermore, the behavioral neurological dysfunctions observed after ischemia in WT mice were significantly ameliorated in KO mice. The ameliorated symptoms observed in KO mice after ischemia were reversed to almost the same severity as WT mice by intracerebroventricular injection of PGE 2 into KO mice. Our observations suggest that mPGES-1 may be a critical determinant of postischemic neurological dysfunctions and a valuable therapeutic target for treatment of human stroke. |
| Databáze: | OpenAIRE |
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