12/15-Lipoxygenase inhibitor baicalein suppresses PPARγ expression and nuclear translocation induced by cerebral ischemia/reperfusion

Accumulating evidences have demonstrated the beneficial actions of peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ protein expression and translocation from the cytoplasm into the nucleus in a time-dependent manner. We also found that PPARγ agonist rosiglitazone enhanced whereas PPARγ antagonist GW9662 inhibited the alteration of PPARγ stimulated by I/R, suggesting that the changes of PPARγ may result from the activation by endogenous ligands. Moreover, the link between the 12/15-lipoxygenase and the production of activating ligands for PPARγ 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 PPARγ alteration was reversed by baicalein, the specific inhibitor of 12/15-lipoxygenase. Baicalein treatment significantly inhibited the up-regulation of PPARγ expression and, furthermore, suppressed PPARγ nuclear accumulation as well as maintained PPARγ cytoplasmic retention. Together, these results suggest that I/R induces both PPARγ expression and translocation, probably through the activation by endogenous ligands in a 12/15-lipoxygenase inhibitor-sensitive way.