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


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.
Lin
Teng-Nan
TN
Neuroscience Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Cheung
Wai-Mui
WM
Wu
Jui-Sheng
JS
Chen
Jean-Ju
JJ
Lin
Heng
H
Chen
Jin-Jer
JJ
Liou
Jun-Yang
JY
Shyue
Song-Kun
SK
Wu
Kenneth K
KK
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control / Q000628:therapy*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
C477819:15-deoxyprostaglandin J2; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D051547:Heme Oxygenase-1; D051545:Cyclooxygenase 1; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D015230:Prostaglandin D2