Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D(3) or 9-cis-retinoic acid in undifferentiated THP-1 cells

J Lipid Res. 2001 Feb;42(2):181-7.

Abstract

We have previously shown that acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) protein content increases significantly during the human monocyte-macrophage differentiation process. To gain further insight, we used undifferentiated human monocytic THP-1 cells as a model system with which to examine whether ACAT-1 mRNA and protein content can be increased by treating cells with 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] or with 9-cis-retinoic acid (9-cis-RA), two agents known to upregulate the expression of various genes during the monocyte-macrophage differentiation process. Immunoblot analysis with anti-human ACAT-1 antibodies revealed that ACAT-1 protein was increased by 2.6-fold, using 1,25-(OH)(2)D(3) at a physiological concentration (100 pM). ACAT-1 protein was also increased when using 9-cis-RA, but only at relatively high concentrations (0.1;-1 microM). Northern blot analysis revealed that among the four ACAT-1 mRNA transcripts (2.8, 3.6, 4.2, and 7.0 kb) examined, only the 2.8- and 3.6-kb transcripts were selectively increased. On the basis of enzyme assays in vitro, ACAT activity was increased 3.0-fold by using 100 nM 1,25-(OH)(2)D(3), and 1.8-fold by using 1 microM 9-cis-RA. Together, our results suggest that 1,25-(OH)(3) participates in ACAT-1 gene expression during the monocyte-macrophage differentiation process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alitretinoin
  • Base Sequence
  • Blotting, Northern
  • Calcitriol / pharmacology*
  • Cell Differentiation
  • Cell Line
  • DNA Primers
  • Enzyme Induction
  • Humans
  • Monocytes / drug effects*
  • Monocytes / enzymology
  • RNA, Messenger / genetics
  • Sterol O-Acyltransferase / biosynthesis*
  • Sterol O-Acyltransferase / genetics
  • Tretinoin / pharmacology*

Substances

  • DNA Primers
  • RNA, Messenger
  • Alitretinoin
  • Tretinoin
  • Sterol O-Acyltransferase
  • Calcitriol