T33, a novel peroxisome proliferator-activated receptor y/α agonist, exerts neuroprotective action via its anti-inflammatory activities

	T33, a novel peroxisome proliferator-activated receptor y/α agonist, exerts neuroprotective action via its anti-inflammatory activities
	Wang Ying; Yang Yushe; Tang Xican; Zhang Haiyan
刊名	Acta Pharmacologica Sinica
	2011
卷号	32 期号:9 页码:1100
关键词	stroke middle cerebral artery occlusion oxygen-glucose deprivation astrocytes BV-2 cells inflammation nuclear factorkappa B T33 peroxisome proliferator-activated receptor y
ISSN号	1671-4083
英文摘要	Aim: To examine the neuroprotective effects of T33, a peroxisome proliferator-activated receptor gamma/alpha (PPARy/α) agonist, in acute ischemic models in vitro and in vivo. Methods: Primary astrocytes subjected to oxygen-glucose deprivation/reperfusion (O/R) and BV-2 cells subjected to hypoxia were used as a model simulating the ischemic core and penumbra, respectively. The mRNA levels of tumor necrosis factor-a (TNF-α) and interleukin-lβ (IL-11) were measured using qPCR. The levels of TNF-a secreted by BV-2 cells were measured using ELISA. Protein levels of cyclooxygenase-2 (COX-2), p65, phosphorylated l-KBa/l-KBa, phosphorylated I-KB kinase (plKK), phosphorylated eukaryote initiation factor 2α (p-elF-2a)/elF-2a and p-p38/p38 were detected using Western blot. PPARy activity was measured using EMSA. The neuroprotection in vivo was examined in rat middle cerebral artery occlusion (MCAO) model with neurological scoring and TTC staining. Results: Addition of T33 (0.5 μmol/L) increased the level of I-KBα protein in primary astrocytes subjected to O/R, which was due to promoting protein synthesis without affecting degradation. In primary astrocytes subjected to O/R, addition of T33 amplified I-KBα gene transcription and mRNA translation, thus suppressing the nuclear factor-kappa B (NF-KB) pathway and reducing inflammatory mediators (TNF-a, IL-1β, and COX-2). In BV-2 cells subjected to hypoxia, T33 (0.5 μmol/L) reduced TNF-a, COX-2, and p-P38 production, which was antagonized by pre-administration of the specific PPARy antagonist GW9662 (30 μmol/L). T33 (2 mg/kg, ip) attenuated MCAO-induced inflammatory responses and brain infarction, which was antagonized by pre-administered GW9662 (4 mg/kg, ip). Conclusion: T33 exerted anti-inflammatory effects in the ischemic core and penumbra via PPARy activation, which contributed to its neuroprotective action.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/294941]
专题	中国科学院上海药物研究所
作者单位	中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Wang Ying,Yang Yushe,Tang Xican,et al. T33, a novel peroxisome proliferator-activated receptor y/α agonist, exerts neuroprotective action via its anti-inflammatory activities[J]. Acta Pharmacologica Sinica,2011,32(9):1100.
APA	Wang Ying,Yang Yushe,Tang Xican,&Zhang Haiyan.(2011).T33, a novel peroxisome proliferator-activated receptor y/α agonist, exerts neuroprotective action via its anti-inflammatory activities.Acta Pharmacologica Sinica,32(9),1100.
MLA	Wang Ying,et al."T33, a novel peroxisome proliferator-activated receptor y/α agonist, exerts neuroprotective action via its anti-inflammatory activities".Acta Pharmacologica Sinica 32.9(2011):1100.