12/15-Lipoxygenase inhibitor baicalein suppresses PPAR gamma expression and nuclear translocation induced by cerebral ischemia/reperfusion.
Accumulating evidences have demonstrated the beneficial actions of peroxisome proliferator-activated receptor gamma (PPAR gamma) in a variety of animal stroke models. Following middle cerebral artery occlusion (60 min) and 2-24 hr reperfusion in rats, we observed cerebral ischemia/reperfusion (I/R) induced up-regulation of PPAR gamma protein expression and translocation from the cytoplasm into the nucleus in a time-dependent manner. We also found that PPAR gamma agonist rosiglitazone enhanced whereas PPAR gamma antagonist GW9662 inhibited the alteration of PPAR gamma stimulated by I/R, suggesting that the changes of PPAR gamma may result from the activation by endogenous ligands. Moreover, the link between the 12/15-lipoxygenase and the production of activating ligands for PPAR gamma has been proved in various tissues. However, the relation of them in brain tissue has not been identified. We demonstrated that the I/R-induced PPAR gamma alteration was reversed by baicalein, the specific inhibitor of 12/15-lipoxygenase. Baicalein treatment significantly inhibited the up-regulation of PPAR gamma expression and, furthermore, suppressed PPAR gamma nuclear accumulation as well as maintained PPAR gamma cytoplasmic retention. Together, these results suggest that I/R induces both PPAR gamma expression and translocation, probably through the activation by endogenous ligands in a 12/15-lipoxygenase inhibitor-sensitive way.
Xu
Yan-Wei
YW
Tianjin Neurology Institute, Tianjin Medical University General Hospital, 154 Anshan Road Heping District, Tianjin 300052, China.
Sun
Li
L
Liang
Hao
H
Sun
Guo-Min
GM
Cheng
Yan
Y
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D044950:Flavanones / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000975:Antioxidants; D044950:Flavanones; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C006680:baicalein