Teruel T, Clapham J C, Smith S A
Department of Vascular Biology, SmithKline Beecham Pharmaceuticals, Harlow, CM19 5AW, United Kingdom.
Biochem Biophys Res Commun. 1999 Oct 22;264(2):311-5. doi: 10.1006/bbrc.1999.1526.
Rodent brown adipocytes express peroxisome proliferator activated receptor-alpha (PPARalpha) and PPARgamma and while the rodent uncoupling protein-1 (UCP-1) gene contains a putative peroxisome proliferator response element (PPRE), only PPARgamma activation by thiazolidinediones increase UCP-1 mRNA levels. We have investigated this phenomenon in foetal rat brown adipocytes (FBA) and show that although transactivation occurs in FBA containing a plasmid encoding 4.5kb of the 5'-flanking region of the rat UCP-1 promoter ((-4551)-UCP-1-CAT) treated with either the selective PPARgamma agonist rosiglitazone (1.0 microM) or the selective PPARalpha agonist Wy 14643 (10.0 microM), only rosiglitazone induced transcription of UCP-1 mRNA. Furthermore, Wy 14643 (10 and 100.0 microM) abolished rosiglitazone-induced UCP-1 mRNA induction in spite of a transactivation event occurring with the combination treatment. Thus in FBA PPARalpha-activation with Wy 14643 elicits a "blind" transactivation of the UCP-1 promoter which can prevent PPARgamma-mediated UCP-1 mRNA transcription either by competition for the PPRE or by an unidentified post-transcriptional event.
啮齿动物棕色脂肪细胞表达过氧化物酶体增殖物激活受体-α（PPARα）和PPARγ，虽然啮齿动物解偶联蛋白-1（UCP-1）基因含有一个假定的过氧化物酶体增殖物反应元件（PPRE），但只有噻唑烷二酮类药物激活PPARγ才能增加UCP-1 mRNA水平。我们在胎鼠棕色脂肪细胞（FBA）中研究了这一现象，结果表明，虽然在用选择性PPARγ激动剂罗格列酮（1.0微摩尔）或选择性PPARα激动剂Wy 14643（10.0微摩尔）处理的含有编码大鼠UCP-1启动子5'-侧翼区4.5kb的质粒（（-4551）-UCP-1-CAT）的FBA中发生了反式激活，但只有罗格列酮诱导了UCP-1 mRNA的转录。此外，尽管联合处理时发生了反式激活事件，但Wy 14643（10和100.0微摩尔）消除了罗格列酮诱导的UCP-1 mRNA诱导。因此，在FBA中，用Wy 14643激活PPARα会引发UCP-1启动子的“盲目”反式激活，这可能通过竞争PPRE或通过未确定的转录后事件来阻止PPARγ介导的UCP-1 mRNA转录。
