Gene expression of acyl coenzyme A: Cholesterol acyltransferase is upregulated in human monocytes during differentiation and foam cell formation

Hongxing Wang, Sandra J. Germain, Pamela P. Benfield, Peter J. Gillies

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)809-814
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume16
Issue number6
DOIs
StatePublished - 1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Keywords

  • foam cell
  • human acyl coenzyme A:cholesterol acyltransferase
  • mRNA
  • macrophage
  • monocyte

Fingerprint

Dive into the research topics of 'Gene expression of acyl coenzyme A: Cholesterol acyltransferase is upregulated in human monocytes during differentiation and foam cell formation'. Together they form a unique fingerprint.

Cite this