Cholesterol ester formation in cultured human fibroblasts. Stimulation by oxygenated sterols.
Open accessAbstract
Incubation of monolayers of cultured human fibroblasts with oxygenated sterols (25-hydroxycholesterol, 7-ketocholesterol, or 6-ketocholestanol) markedly enhanced the rate at which the cells esterified their endogenous cholesterol and produced an increase in the cellular content of cholesterol esters. The enhanced esterification capacity was associated with an increase in the activity of a membrane-bound fatty acyl-CoA:cholesteryl acyltransferase. Incubation of cells for 5 hours with 5 mug/ml of 25-hydroxycholesterol produced an 8-fold increase in the specific activity of this enzyme when assayed in cell-free extracts. Since the oxygenated sterols that elevated the activity of fatty acyl-CoA:cholesteryl acyl-transferase also suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the data suggest that the processes of cholesterol ester formation and cholesterol synthesis in human fibroblasts are regulated in a reciprocal manner by coordinate changes in the activities of these two membrane-bound enzymes.
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Cholesterol ester formation is greatly enhanced by 25HC by activation of fatty acyl coA:cholesterol acyl transferase enzyme in human fibroblasts and other cells.
“Cholesterol ester formation is greatly enhanced by 25HC by the activation of fatty acyl coA:cholesterol acyl transferase enzyme in human fibroblasts (46) and other cells.”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [46]
Previous studies have shown that 25HC activates cholesterol esterification by SOAT (also known as ACAT).
“Previous studies have shown that 25HC activates cholesterol esterification by SOAT (also known as ACAT) (46).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [46]
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Brown, M. S., Ho, Y. K., & Goldstein, J. L. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70568-7 · Cited by 722 · see citing works
Self-citationLu, F., Liang, Q., Abi-Mosleh, L., Das, A., De Brabander, J. K., Goldstein, J. L., & Brown, M. S. (2015) · eLife · doi:10.7554/elife.12177 · Cited by 333 · see citing works
Self-citationBROWN, M. S., KOVANEN, P. T., & GOLDSTEIN, J. L. (1979) · Proceedings of the 1978 Laurentian Hormone Conference · doi:10.1016/b978-0-12-571135-7.50009-6 · Cited by 311 · see citing works
Self-citationTHE LDL RECEPTOR LOCUS AND THE GENETICS OF FAMILIAL HYPERCHOLESTEROLEMIA
Goldstein, J. L., & Brown, M. S. (1979) · Annual Review of Genetics · doi:10.1146/annurev.ge.13.120179.001355 · Cited by 233 · see citing works
Self-citationCatherine C. Y., C., Chen, J., Thomas, M. A., Cheng, D., Veronica A., D. P., Newton, R. S., Pape, M. E., & Chang, T.-Y. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29532 · Cited by 158 · see citing works
Cashikar, A. G., Toral-Rios, D., Timm, D., Romero, J., Strickland, M., Long, J. M., Han, X., Holtzman, D. M., & Paul, S. M. (2023) · Journal of Lipid Research · doi:10.1016/j.jlr.2023.100350 · Cited by 72 · see citing works
Insulin Regulation of Hepatic Lipid Homeostasis
Uehara, K., Santoleri, D., Whitlock, A. E. G., & Titchenell, P. M. (2023) · Comprehensive Physiology · doi:10.1002/cphy.c220015 · Cited by 49 · see citing works
- Authors
- Brown, M., Dana, S., & Goldstein, J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1975-05
- Volume
- 250
- Issue
- 10
- Pages
- 4025-4027
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1499573413
- Cited by
- 364
- References
- 0
- Citations by year
- 2026: 5 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 8 · 2013: 2 · 2012: 6
- FWCI
- 31.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- human fibroblasts, 25-hydroxycholesterol, 7-ketocholesterol, 6-ketocholestanol, HMGR, cholesterol biosynthesis, enzyme regulation, reciprocal regulation
- MeSH terms
- Acyltransferases, Cells, Cultured, Cholesterol, Esters, Fatty Acids, Fibroblasts, Humans, Hydroxycholesterols, Hydroxymethylglutaryl CoA Reductases, Hydroxysteroids, Hypercholesterolemia, Ketosteroids, Kinetics, Time Factors
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