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

George Cook, Timmye L. Edwards, Michelle S. Jansen, Suleiman Bahouth, Henry G. Wilcox, Edwards Park

Research output: Contribution to journalArticle

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Abstract

Carnitine palmitoyltransferase-I (CPT-I) is a major control point for fatty acid oxidation. Two kinetically different isoforms, CPT-Iα and CPT-Iβ, 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-Iα and CPT-Iβ expression in the heart. Expression of the CPT-Iα gene was very high in the fetal heart and declined following birth. CPT-Iβ was also highly expressed in fetal myocytes and remained so throughout development. CPT-Iα mRNA abundance was increased in both the liver and heart of diabetic or fasted rats, but CPT-Iβ mRNA levels were not altered in these states. A high fat diet elevated expression of the CPT-Iα gene in the liver but not in the heart. The fat content of the diet did not affect the expression of CPT-Iβ. Cultures of neonatal rat cardiac myocytes were transfected with luciferase reporter genes driven by CPT-Iα or CPT-Iβ promoters. Two regions of the CPT-Iα 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-Iα was dependent on Sp1 sites and a CCAAT box in the proximal promoter. Our data indicate that the CPT-Iβ gene is expressed in a tissue specific manner, but that it is not subject to the same developmental or hormonal controls imposed on CPT-Iα. In addition some aspects of CPT-Iα 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-Iα and CPT-Iβ gene expression in the heart and (b) differential regulation of CPT-Iα expression in the heart and liver.

Original languageEnglish (US)
Pages (from-to)317-329
Number of pages13
JournalJournal of Molecular and Cellular Cardiology
Volume33
Issue number2
DOIs
StatePublished - Jan 1 2001

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Carnitine O-Palmitoyltransferase
Protein Isoforms
Genes
Cardiac Myocytes
Liver

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Differential regulation of carnitine palmitoyltransferase-I gene isoforms (CPT-Iα and CPT-Iβ) in the rat heart. / Cook, George; Edwards, Timmye L.; Jansen, Michelle S.; Bahouth, Suleiman; Wilcox, Henry G.; Park, Edwards.

In: Journal of Molecular and Cellular Cardiology, Vol. 33, No. 2, 01.01.2001, p. 317-329.

Research output: Contribution to journalArticle

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