Physiological and therapeutic roles of peroxisome proliferator-activated receptors.
Physiological and therapeutic roles of peroxisome proliferator-activated receptors.
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DOI：
10.1089/15209150260007381
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发表时间：
2002-01-01
影响因子：
5.4
通讯作者：
Wagner, John A
中科院分区：
文献类型：
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作者：
Berger, Joel;Wagner, John A
过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPARs）是一组由不同基因编码的核受体亚型，包括PPARgamma、PPARalpha和PPARdelta。PPARs是配体调节的转录因子，其通过与启动子内的特异性应答元件（PPREs）结合来控制基因表达。PPARs作为异二聚体与类维生素A X受体结合，并且在结合激动剂作用下，与辅因子相互作用，增加转录起始速率。PPARs作为脂质传感器和脂质代谢调节剂发挥着重要的生理作用。PPARs的天然配体包括脂肪酸和类二十烷酸。更有效的合成PPAR配体，包括贝特类和噻唑烷二酮类，在血脂异常和糖尿病的治疗中是有效的。选择性配体的使用导致发现PPARs在病理状态中的额外潜在作用，包括动脉粥样硬化、炎症和高血压。本文综述了PPAR作用的分子机制以及PPARs在几种慢性疾病的病因学和治疗中的作用。
The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms, including PPARgamma, PPARalpha, and PPARdelta, encoded by different genes. PPARs are ligand-regulated transcription factors that control gene expression by binding to specific response elements (PPREs) within promoters. PPARs bind as heterodimers with a retinoid X receptor and, upon binding agonist, interact with cofactors increasing the rate of transcription initiation. The PPARs play a critical physiological role as lipid sensors and regulators of lipid metabolism. Natural ligands for the PPARs include fatty acids and eicosanoids. More potent synthetic PPAR ligands, including the fibrates and thiazolidinediones, are effective in the treatment of dyslipidemia and diabetes. Use of selective ligands led to the discovery of additional potential roles for the PPARs in pathological states, including atherosclerosis, inflammation, and hypertension. This review provides an overview of the molecular mechanisms of PPAR action and the involvement of the PPARs in the etiology and treatment of several chronic diseases.