Mascaró C, Acosta E, Ortiz J A, Marrero P F, Hegardt F G, Haro D
Unit of Biochemistry, School of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.
J Biol Chem. 1998 Apr 10;273(15):8560-3. doi: 10.1074/jbc.273.15.8560.
The expression of several genes involved in intra- and extracellular lipid metabolism, notably those involved in peroxisomal and mitochondrial beta-oxidation, is mediated by ligand-activated receptors, collectively referred to as peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of expression of carnitine palmitoyltransferase (CPT) genes, which are regulated by fatty acids, we have examined the transcriptional regulation of the human MCPT I gene. We have cloned by polymerase chain reaction the 5'-flanking region of this gene and demonstrated its transcriptional activity by transfection experiments with the CAT gene as a reporter. We have also shown that this is a target gene for the action of PPARs, and we have localized a PPAR responsive element upstream of the first exon. These results show that PPAR regulates the entry of fatty acids into the mitochondria, which is a crucial step in their metabolism, especially in tissues like heart, skeletal muscle and brown adipose tissue in which fatty acids are a major source of energy.
参与细胞内和细胞外脂质代谢的几个基因的表达，特别是那些参与过氧化物酶体和线粒体β-氧化的基因，是由配体激活受体介导的，这些受体统称为过氧化物酶体增殖物激活受体（PPARs）。为了更深入了解受脂肪酸调控的肉碱棕榈酰转移酶（CPT）基因的表达控制，我们研究了人MCPT I基因的转录调控。我们通过聚合酶链反应克隆了该基因的5'侧翼区域，并以CAT基因作为报告基因通过转染实验证明了其转录活性。我们还表明这是PPARs作用的靶基因，并且我们在第一个外显子上游定位了一个PPAR反应元件。这些结果表明PPAR调节脂肪酸进入线粒体，这是它们代谢中的关键步骤，特别是在心脏、骨骼肌和棕色脂肪组织等组织中，脂肪酸是主要能量来源。
