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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression.
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Diverse peroxisome proliferator-activated receptors bind to the peroxisome proliferator-responsive elements of the rat hydratase/dehydrogenase and fatty acyl-CoA oxidase genes but differentially induce expression.

机译：不同的过氧化物酶体增殖物激活受体与大鼠水合酶/脱氢酶和脂肪酰基辅酶A氧化酶基因的过氧化物酶体增殖物反应性元件结合但是差异地诱导表达。

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摘要

The ability of peroxisome proliferator-activated receptors (PPARs) to induce expression of a reporter gene linked to a peroxisome proliferator-responsive element (PPRE) from either the rat enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase gene or acyl-CoA oxidase [acyl-CoA:oxygen 2-oxidoreductase, EC 1.3.3.6] gene was examined by transient transfection assays in COS cells. Mouse and rat PPARs, as well as Xenopus PPAR alpha (xPPAR alpha) could induce expression of a reporter gene linked to the hydratase/dehydrogenase PPRE in the presence of the peroxisome proliferators ciprofibrate or Wy-14,643, whereas xPPAR beta and xPPAR gamma were ineffective. A similar induction of expression of a reporter gene linked to the acyl-CoA oxidase PPRE was observed with all PPARs except xPPAR beta. Extracts from cells transfected with PPAR-encoding genes contained factors that bound to both PPREs. In vitro synthesized PPARs could interact weakly with both PPREs; however, binding of each PPAR to both PPREs was significantly increased by the addition of COS cell nuclear extracts, demonstrating that efficient PPAR/DNA binding requires auxiliary cofactors. One cofactor was identified as the 9-cis-retinoic acid receptor, RXR alpha (retinoid X receptor alpha). Cooperative DNA binding and heteromerization between RXR alpha and each of the PPARs could be seen with both PPREs. Our results demonstrate that PPAR/PPRE binding and cooperativity with RXR alpha (and other cofactors) are obligatory but not necessarily sufficient for peroxisome proliferator-dependent transcription induction and that distinct PPREs can selectively mediate induction by particular PPARs.
机译：过氧化物酶体增殖物激活受体（PPAR）诱导与大鼠烯酰辅酶A水合酶/ 3-羟酰基辅酶A脱氢酶基因或酰基辅酶A氧化酶相关的过氧化物酶体增殖物应答元件（PPRE）的报告基因表达的能力[酰基辅酶A：氧2-氧化还原酶，EC 1.3.3.6]基因通过瞬时转染测定法在COS细胞中进行了检查。小鼠和大鼠PPAR以及非洲爪蟾PPAR alpha（xPPAR alpha）可能在过氧化物酶体增殖物ciprofibrate或Wy-14,643的存在下诱导与水合酶/脱氢酶PPRE相关的报告基因的表达，而xPPAR beta和xPPARγ无效。除xPPAR beta以外的所有PPAR均观察到与酰基辅酶A氧化酶PPRE相关的报告基因表达的相似诱导。用PPAR编码基因转染的细胞的提取物包含与两个PPRE结合的因子。体外合成的PPAR可能与两种PPRE相互作用较弱。但是，通过添加COS细胞核提取物，每个PPAR与两个PPRE的结合显着增加，表明有效的PPAR / DNA结合需要辅助辅因子。一种辅助因子被鉴定为9-顺-视黄酸受体RXRα（类维生素X受体α）。两种PPRE均可观察到RXR alpha与每个PPAR之间的合作DNA结合和异聚。我们的结果表明，PPAR / PPRE与RXR alpha（和其他辅助因子）的结合和协同作用是必须的，但不一定足以过氧化物酶体增殖物依赖性转录诱导，并且不同的PPRE可以选择性地介导特定PPAR的诱导。

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