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 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.
Cook
G A
GA
Department of Pharmacology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA. gcook@utmen.edu
Edwards
T L
TL
Jansen
M S
MS
Bahouth
S W
SW
Wilcox
H G
HG
Park
E A
EA
D000367:Age Factors; D000818:Animals; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004041:Dietary Fats / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D005822:Genetic Vectors; D006321:Heart / Q000196:embryology; D006980:Hyperthyroidism / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured
D004041:Dietary Fats; D005227:Fatty Acids; D020033:Protein Isoforms; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D008156:Luciferases; D002334:Carnitine O-Palmitoyltransferase