This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 26/3/481    most recent 01.ATV.0000201933.53964.5bv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lin, T.-N. Articles by Wu, K. K. Search for Related Content PubMed PubMed Citation Articles by Lin, T.-N. Articles by Wu, K. K.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:481.)
© 2006 American Heart Association, Inc.

Vascular Biology

15d-Prostaglandin J₂ Protects Brain From Ischemia-Reperfusion Injury

Teng-Nan Lin; Wai-Mui Cheung; Jui-Sheng Wu; Jean-Ju Chen; Heng Lin; Jin-Jer Chen; Jun-Yang Liou; Song-Kun Shyue; Kenneth K. Wu

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.

Correspondence to Kenneth K. Wu, Vascular Biology Research Center, Institute of Molecular Medicine and Division of Hematology, University of Texas-Houston Health Science Center, 6431 Fannin, MSB 5.016, Houston, TX 77030. E-mail Kenneth.K.Wu{at}uth.tmc.edu or Teng-Nan Lin bmltn@ibms.sinica.edu.tw

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.

Adv-COX-1 gene transfer increased 15d-PGJ₂ in ischemic brain accompanied by reduced infarct volume, activated caspase 3, and enhanced heme oxygenase-1 and peroxisome proliferator activated receptor (PPAR) expression. 15d-PGJ₂ and rosiglitazone inhibited neuronal apoptosis and necrosis in a PPAR-dependent manner.

Key Words: COX-1 • 15d-PGJ₂ • PPAR • apoptosis • stroke

This article has been cited by other articles:

				O. De Backer, E. Elinck, E. Priem, L. Leybaert, and R. A. Lefebvre Peroxisome Proliferator-Activated Receptor {gamma} Activation Alleviates Postoperative Ileus in Mice by Inhibition of Egr-1 Expression and Its Downstream Target Genes J. Pharmacol. Exp. Ther., November 1, 2009; 331(2): 496 - 503. [Abstract] [Full Text] [PDF]

				M. Sobrado, M. P. Pereira, I. Ballesteros, O. Hurtado, D. Fernandez-Lopez, J. M. Pradillo, J. R. Caso, J. Vivancos, F. Nombela, J. Serena, et al. Synthesis of Lipoxin A4 by 5-Lipoxygenase Mediates PPAR{gamma}-Dependent, Neuroprotective Effects of Rosiglitazone in Experimental Stroke J. Neurosci., March 25, 2009; 29(12): 3875 - 3884. [Abstract] [Full Text] [PDF]

				J.-S. Wu, W.-M. Cheung, Y.-S. Tsai, Y.-T. Chen, W.-H. Fong, H.-D. Tsai, Y.-C. Chen, J.-Y. Liou, S.-K. Shyue, J.-J. Chen, et al. Ligand-Activated Peroxisome Proliferator-Activated Receptor-{gamma} Protects Against Ischemic Cerebral Infarction and Neuronal Apoptosis by 14-3-3{epsilon} Upregulation Circulation, March 3, 2009; 119(8): 1124 - 1134. [Abstract] [Full Text] [PDF]

				M. Collino, N. S.A. Patel, and C. Thiemermann Review: PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury Therapeutic Advances in Cardiovascular Disease, June 1, 2008; 2(3): 179 - 197. [Abstract] [PDF]

				D. A. Andersson, C. Gentry, S. Moss, and S. Bevan Transient Receptor Potential A1 Is a Sensory Receptor for Multiple Products of Oxidative Stress J. Neurosci., March 5, 2008; 28(10): 2485 - 2494. [Abstract] [Full Text] [PDF]

				C. Yang, S.-H. Jo, B. Csernus, E. Hyjek, Y. Liu, A. Chadburn, and Y. L. Wang Activation of Peroxisome Proliferator-Activated Receptor {gamma} Contributes to the Survival of T Lymphoma Cells by Affecting Cellular Metabolism Am. J. Pathol., February 1, 2007; 170(2): 722 - 732. [Abstract] [Full Text] [PDF]