Cook G A, Edwards T L, Jansen M S, Bahouth S W, Wilcox H G, Park E A
Department of Pharmacology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
J Mol Cell Cardiol. 2001 Feb;33(2):317-29. doi: 10.1006/jmcc.2000.1304.
Carnitine palmitoyltransferase-I (CPT-I) is a major control point for fatty acid oxidation. Two kinetically different isoforms, CPT-I alpha and CPT-I beta, have been identified. Cardiac ventricular myocytes are the only cells known to express both CPT-I isoforms. In this study, we characterized the differential regulation of CPT-I alpha and CPT-I beta expression in the heart. Expression of the CPT-I alpha gene was very high in the fetal heart and declined following birth. CPT-I beta was also highly expressed in fetal myocytes and remained so throughout development. CPT-I alpha mRNA abundance was increased in both the liver and heart of diabetic or fasted rats, but CPT-I beta mRNA levels were not altered in these states. A high fat diet elevated expression of the CPT-I alpha gene in the liver but not in the heart. The fat content of the diet did not affect the expression of CPT-I beta. Cultures of neonatal rat cardiac myocytes were transfected with luciferase reporter genes driven by CPT-I alpha or CPT-I beta promoters. Two regions of the CPT-I alpha promoter, including an upstream region (-1300/-960) and a region in the proximal promoter (-193/-52) contributed equally to basal expression in cardiac myocytes. Basal transcription of CPT-I alpha was dependent on Sp1 sites and a CCAAT box in the proximal promoter. Our data indicate that the CPT-I beta gene is expressed in a tissue specific manner, but that it is not subject to the same developmental or hormonal controls imposed on CPT-I alpha. In addition some aspects of CPT-I alpha expression are confined to the liver. The data presented here thus suggest that two types of differential regulation of CPT-I genes exist: (a) differential control of CPT-I alpha and CPT-I beta gene expression in the heart and (b) differential regulation of CPT-I alpha expression in the heart and liver.
肉碱棕榈酰转移酶-I（CPT-I）是脂肪酸氧化的主要控制点。已鉴定出两种动力学不同的同工型，即CPT-Iα和CPT-Iβ。心脏心室肌细胞是已知同时表达这两种CPT-I同工型的唯一细胞。在本研究中，我们对心脏中CPT-Iα和CPT-Iβ表达的差异调节进行了表征。CPT-Iα基因在胎儿心脏中表达非常高，出生后下降。CPT-Iβ在胎儿心肌细胞中也高度表达，并在整个发育过程中保持如此。糖尿病或禁食大鼠的肝脏和心脏中CPT-IαmRNA丰度增加，但在这些状态下CPT-IβmRNA水平未改变。高脂饮食可提高肝脏中CPT-Iα基因的表达，但对心脏无影响。饮食中的脂肪含量不影响CPT-Iβ的表达。用由CPT-Iα或CPT-Iβ启动子驱动的荧光素酶报告基因转染新生大鼠心肌细胞培养物。CPT-Iα启动子的两个区域，包括上游区域（-1300/-960）和近端启动子中的一个区域（-193/-52）对心肌细胞中的基础表达贡献相同。CPT-Iα的基础转录依赖于近端启动子中的Sp1位点和一个CCAAT框。我们的数据表明，CPT-Iβ基因以组织特异性方式表达，但它不受施加于CPT-Iα的相同发育或激素控制。此外，CPT-Iα表达的某些方面仅限于肝脏。因此，此处呈现的数据表明存在两种类型的CPT-I基因差异调节：（a）心脏中CPT-Iα和CPT-Iβ基因表达的差异控制，以及（b）心脏和肝脏中CPT-Iα表达的差异调节。
