Differential regulation of carnitine palmitoyltransferase-I gene isoforms (CPT-I alpha and CPT-I beta) in the rat heart

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 hea rt, 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 my ocytes and remained so throughout development. CPT-beta mRNA abundance was increased in both the liver and heart of diabetic or fasted rats, but CTT-I beta mRNA levels were not altered in these states. A high fat diet elevate d 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. Cultu res of neonatal rat cardiac myocytes were transfected with luciferase repor ter 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 regi on in the proximal promoter (-193/-52) contributed equally to basal express ion in cardiac myocytes. Basal transcription of CPT-I beta 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 CP T-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 differ ential regulation of CPT-I genes exist: (a) differential control of CPT-I a lpha and CPT-I beta gene expression in the heart and (b) differential regul ation of CPT-I alpha expression in the heart and liver, (C) 2001 Academic P ress.