15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-gamma, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPARgamma is linked to anti-inflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) acts as a physiologic agonist for PPARgamma. In this study, we found that injection of 15d-PGJ2 into the locus of striatal hematoma increased PPARgamma-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ2 significantly reduced nuclear factor-kappaB (NF-kappaB) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d-PGJ2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ2 at the onset of ICH is associated with activation of PPARgamma and elevation of catalase expression, suppression of NF-kappaB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.
Zhao
Xiurong
X
Stroke Program, Department of Neurology, University of Texas - Houston Medical School, Houston, Texas 77030, USA.
Zhang
Yujian
Y
Strong
Roger
R
Grotta
James C
JC
Aronowski
Jaroslaw
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D002374:Catalase / Q000096:biosynthesis / Q000187:drug effects*; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D024202:Electrophoretic Mobility Shift Assay; D015870:Gene Expression / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000188:drug therapy*; D007276:Injections, Intraventricular; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction
C477819:15-deoxyprostaglandin J2; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D002374:Catalase; D015230:Prostaglandin D2