In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 75, No. 4 ( 1978-04), p. 1877-1881
Abstract:
The synthesis of cholesteryl esters in cultured human fibroblasts is catalyzed by a microsomal acyl-coenzyme A:cholesterol acyltransferase (EC 2.3.1.26). The acyltransferase activity is enhanced when fibroblasts take up cholesterol contained in plasma low density lipoprotein. In the current studies two steroids, SC-31769 (an analogue of 7-ketocholesterol) and progesterone, were shown to inhibit acyltransferase activity in cell-free extracts of human fibroblasts. When added to intact cells, these steroids inhibited the incorporation of [ 14 C]oleate into cellular cholesteryl [ 14 C]oleate and reduced the accumulation of cholesteryl esters in fibroblasts exposed to low density lipoprotein. The inhibition of cholesteryl ester formation in intact cells by SC-31769 and progesterone was readily reversible. Neither compound inhibited the incorporation of [ 14 C]oleate into [ 14 C]triglycerides or [ 14 C]phospholipids. When incubated with fibroblast monolayers at a concentration of 1 μg/ml, SC-31769 suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase [mevalonate:NADP + oxidoreductase (CoA-acylating); EC 1.1.1.34], the rate-controlling enzyme in cholesterol synthesis. In contrast, progesterone had no effect on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity at concentrations as high as 25 μg/ml. The availability of two types of steroid compounds that inhibit the acyltransferase activity and cholesteryl ester synthesis in human fibroblasts should prove useful in further studies of the regulatory mechanisms responsible for cholesteryl ester accumulation in human cells under normal and pathologic conditions.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.75.4.1877
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1978
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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