15d-prostaglandin J2 protects brain from ischemia-reperfusion injury.

Abstract

OBJECTIVE:

Brain expresses abundant lipocalin-type prostaglandin (PG) D2 (PGD2) synthase but the role of PGD2 and its metabolite, 15-deoxy-Delta(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-gamma (PPARgamma) and heme oxygenase-1 (HO-1). Intraventricular infusion of 15d-PGJ2 resulted in reduction of infarct volume, which was abrogated by a PPARgamma 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 PPARgamma and HO-1 expression. The anti-apoptotic effect was abrogated by PPARgamma inhibition.

CONCLUSIONS:

15d-PGJ2 suppressed ischemic brain infarction and neuronal apoptosis and necrosis in a PPARgamma dependent manner. 15d-PGJ2 may play a role in controlling acute brain damage induced by ischemia-reperfusion.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 26 Issue 3 Pg. 481-7 (Mar 2006) ISSN: 1524-4636 [Electronic] United States
• PMID: 16385084 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxyprostaglandin J2
• Neuroprotective Agents
• PPAR gamma
• Thiazolidinediones
• Vasodilator Agents
• Rosiglitazone
• Heme Oxygenase-1
• Cyclooxygenase 1
• CASP3 protein, human
• Casp3 protein, rat
• Caspase 3
• Caspases
• Prostaglandin D2

Topics

• Adenoviridae (genetics)
• Animals
• Apoptosis (drug effects, physiology)
• Caspase 3
• Caspases (metabolism)
• Cells, Cultured
• Cyclooxygenase 1 (genetics, metabolism)
• Gene Transfer Techniques
• Genetic Therapy
• Heme Oxygenase-1 (genetics, metabolism)
• Infarction, Middle Cerebral Artery (metabolism, therapy)
• Male
• Necrosis
• Neurons (pathology)
• Neuroprotective Agents (metabolism)
• PPAR gamma (genetics, metabolism)
• Prostaglandin D2 (analogs & derivatives, metabolism)
• Rats
• Rats, Long-Evans
• Reperfusion Injury (metabolism, prevention & control, therapy)
• Rosiglitazone
• Thiazolidinediones (pharmacology)
• Vasodilator Agents (pharmacology)