Gene Expression of Acyl Coenzyme A

Author:

Wang Hongxing1,Germain Sandra J.1,Benfield Pamela P.1,Gillies Peter J.1

Affiliation:

1. From the DuPont Merck Research Laboratories, Cardiovascular Diseases Research, Wilmington, Del.

Abstract

Abstract The gene expression and enzyme kinetics of acyl coenzyme A:cholesterol acyltransferase (ACAT) were investigated in human monocytes, macrophages, and foam cells. Northern blot analysis using a 1.65-kb coding region of human ACAT cDNA as the probe showed that each of the cell types exhibited four mRNA transcripts. The levels of the 4.2- and 3.7-kb ACAT transcripts were three- and sixfold higher, respectively, in macrophages than monocytes. These transcripts were expressed at the same high levels after conversion of macrophages to foam cells. In contrast, the 6.3- and 4.4-kb transcripts for ACAT were expressed at a relatively constant level in all three cell types. The expression of mRNA for glyceraldehyde phosphate dehydrogenase, the control gene in this study, was also expressed at a constant level in each of the cell types. The increase in ACAT mRNA was accompanied by changes in the kinetic properties of the enzyme. Specifically, there was a 14-fold increase in V max and a 71% decrease in K m with respect to oleoyl coenzyme A. Although not definitive, the concomitant changes in mRNA and V max strongly suggest that the amount of ACAT protein increases upon conversion of monocytes to macrophages. The data show that ACAT in monocytes can be regulated by both substrate and gene expression.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

Reference21 articles.

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2. Bell FP. Arterial cholesterol esterification by acylCoA-cholesterol acyltransferase: its possible significance in atherogenesis and its inhibition by drugs. In: Fears R ed. Pharmacological Control of Hyperlipidaemia . Barcelona Spain: JR Prous Science Publishers SA; 1986:409-422.

3. Billheimer JT Gillies PJ. Intracellular cholesterol esterification. In: Esfahani M Swaney J eds. Advances in Cholesterol Research . Caldwell NJ: Telford Press; 1990:7-45.

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