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

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Objective - Brain expresses abundant lipocalin-type prostaglandin (PG) D2 (PGD2) synthase but the role of PGD2 and its metabolite, 15-deoxy-Δ12,14 PGJ2 (15d-PGJ 2) 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-γ (PPARγ) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d-PGJ2 resulted in reduction of infarct volume, which was abrogated by a PPARγ 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 PPARγ and HO-1 expression. The anti-apoptotic effect was abrogated by PPARγ inhibition. Conclusion - 15d-PGJ2 suppressed ischemic brain infarction and neuronal apoptosis and necrosis in a PPARγ dependent manner. 15d-PGJ2 may play a role in controlling acute brain damage induced by ischemia-reperfusion.

Original languageEnglish
Pages (from-to)481-487
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 2006
Externally publishedYes

Keywords

  • 15d-PGJ
  • Apoptosis
  • COX-1
  • PPARγ
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Lin, T. N., Cheung, W. M., Wu, J. S., Chen, J. J., Lin, H., Chen, J. J., Liou, J. Y., Shyue, S. K., & Wu, K. K. (2006). 15d-prostaglandin J2 protects brain from ischemia-reperfusion injury. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(3), 481-487. https://doi.org/10.1161/01.ATV.0000201933.53964.5b