on December 29, 2005
Published online before print December 29, 2005, doi: 10.1161/01.ATV.0000201933.53964.5b
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Submitted on October 28, 2005
Accepted on November 21, 2005
15d-Prostaglandin J2 Protects Brain From Ischemia-Reperfusion Injury
Teng-Nan Lin ;
From Neuroscience Division (T.-N.L., W.-M.C., J.-S.W., J.-J.C., H.L., J.-J.Chen, S.-K.S.), Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Vascular Biology Research Center (J.-Y.L., K.K.W.), Institute of Molecular Medicine and Division of Hematology, University of Texas-Houston Health Science Center, Houston, Tex.
* To whom correspondence should be addressed. E-mail: Kenneth.K.Wu{at}uth.tmc.edu.
Objective--Brain expresses abundant lipocalin-type prostaglandin (PG) D2 (PGD2) synthase but the role of PGD2 and its metabolite, 15-deoxy-
12,14 PGJ2 (15d-PGJ2) in brain protection is unclear. The aim of this study is to assess the effect of 15d-PGJ2 on neuroprotection.
Methods and Results--Adenoviral transfer of cyclooxygenase-1 (Adv-COX-1) was used to amplify the production of 15d-PGJ2 in ischemic cortex in a rat focal infarction model. Cortical 15d-PGJ2 in Adv-COX-1-treated rats was increased by 3-fold over control, which was correlated with reduced infarct volume and activated caspase 3, and increased peroxisome proliferator activated receptor-
(PPAR) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d-PGJ2 resulted in reduction of infarct volume, which was abrogated by a PPAR inhibitor. Rosiglitazone infusion had a similar effect. 15d-PGJ2 and rosiglitazone at low concentrations suppressed H2O2-induced rat or human neuronal apoptosis and necrosis and induced PPAR and HO-1 expression. The anti-apoptotic effect was abrogated by PPAR inhibition.
Conclusion--15d-PGJ2 suppressed ischemic brain infarction and neuronal apoptosis and necrosis in a PPAR dependent manner. 15d-PGJ2 may play a role in controlling acute brain damage induced by ischemia-reperfusion.
Key words: COX-1 • 15d-PGJ2 • PPAR
•
apoptosis •
stroke
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