T33, a novel peroxisome proliferator-activated receptor gamma/alpha agonist, exerts neuroprotective action via its anti-inflammatory activities
文献类型：期刊论文
| 作者 | Wang, Ying; Yang, Yu-she ; Tang, Xi-can; Zhang, Hai-yan
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2011-09 |
| 卷号 | 32期号:9页码:1100-1108 |
| 关键词 | stroke middle cerebral artery occlusion oxygen-glucose deprivation astrocytes BV-2 cells inflammation nuclear factor-kappa B T33 peroxisome proliferator-activated receptor gamma |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2011.69 |
| 文献子类 | Article |
| 英文摘要 | Aim: To examine the neuroprotective effects of T33, a peroxisome proliferator-activated receptor gamma/alpha (PPAR gamma/alpha) 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-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 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 I-kappa B alpha/I-kappa B alpha, phosphorylated I-kappa B kinase (pIKK), phosphorylated eukaryote initiation factor 2 alpha (p-eIF-2 alpha)/eIF-2 alpha and p-p38/p38 were detected using Western blot. PPAR. 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 mu mol/L) increased the level of I-kappa B alpha 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-kappa B alpha gene transcription and mRNA translation, thus suppressing the nuclear factor-kappa B (NF-kappa B) pathway and reducing inflammatory mediators (TNF-alpha, IL-1 beta, and COX-2). In BV-2 cells subjected to hypoxia, T33 (0.5 mu mol/L) reduced TNF-alpha, COX-2, and p-P38 production, which was antagonized by pre-administration of the specific PPAR. antagonist GW9662 (30 mu mol/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 PPAR. activation, which contributed to its neuroprotective action. |
| WOS关键词 | NF-KAPPA-B ; FOCAL CEREBRAL-ISCHEMIA ; PPAR-GAMMA ; INFLAMMATORY RESPONSE ; ARTERY OCCLUSION ; RAT MODEL ; STROKE ; INJURY ; EXPRESSION ; BRAIN |
| 资助项目 | National Natural Science Foundation of China[30801402] ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry[00000000] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2009ZX09301-001] ; National Science & Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2009ZX09301-063] ; Shanghai Science and Technology Development Fund[10QA1408100] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:4335556 |
| WOS记录号 | WOS:000294495700004 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278421]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Zhang, Hai-yan |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Ying,Yang, Yu-she,Tang, Xi-can,et al. T33, a novel peroxisome proliferator-activated receptor gamma/alpha agonist, exerts neuroprotective action via its anti-inflammatory activities[J]. ACTA PHARMACOLOGICA SINICA,2011,32(9):1100-1108. |
| APA | Wang, Ying,Yang, Yu-she,Tang, Xi-can,&Zhang, Hai-yan.(2011).T33, a novel peroxisome proliferator-activated receptor gamma/alpha agonist, exerts neuroprotective action via its anti-inflammatory activities.ACTA PHARMACOLOGICA SINICA,32(9),1100-1108. |
| MLA | Wang, Ying,et al."T33, a novel peroxisome proliferator-activated receptor gamma/alpha agonist, exerts neuroprotective action via its anti-inflammatory activities".ACTA PHARMACOLOGICA SINICA 32.9(2011):1100-1108. |
入库方式： OAI收割
来源：上海药物研究所
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