J. Lipid Res.  Neurobiology of Lipids (ISSN1683-5506)
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Journal of Lipid Research, Vol. 42, 181-187, February 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D3 or 9-cis-retinoic acid in undifferentiated THP-1 cells

Kyu Kyu Maunga, Akira Miyazakia, Hisayuki Nomiyamaa, Catherine C. Y. Changb, Ta-Yuan Changb, and Seikoh Horiuchia
a Department of Biochemistry, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
b Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755

Correspondence to: Akira Miyazaki, To whom correspondence should be addressed., akiramyz{at}kaiju.medic.kumamoto-u.ac.jp (E-mail)

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 D3 [1,25-(OH)2D3] 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)2D3 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 µM). 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)2D3, and 1.8-fold by using 1 µM 9-cis-RA.

Together, our results suggest that 1,25-(OH)3 participates in ACAT-1 gene expression during the monocyte-macrophage differentiation process. Maung, K. K., A. Miyazaki, H. Nomiyama, C. C. Y. Chang, T-Y. Chang, and S. Horiuchi. Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D3 or 9-cis-retinoic acid in undifferentiated THP-1 cells. J. Lipid Res. 2001. 42: 181;–187.

Supplementary key words: ACAT, ACAT-1, monocyte-macrophage differentiation


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