Complete Inhibition of Mouse Macrophage-Derived Foam Cell Formation by Triacsin C
Abstract
Primary mouse peritoneal macrophages effectively take up and metabolize phosphatidylcholine/cholesterol liposomes containing a small amount of phosphatidylserine, which results in the massive accumulation in the cytoplasm of oil red O positive lipid droplets consisting of cholesteryl ester (CE) and triacylglycerol (TG) [Nishikawa et al. (1990) J. Biol. Chem. 265, 5226-5231]. A number of inhibitors of CE synthesis have been reported, but their effects on the lipid droplet formation have not been fully examined. Furthermore, the contribution of TG synthesis to lipid droplet formation has been poorly investigated. We have investigated the relationship between CE and TG syntheses and cytosolic lipid droplet formation in macrophages cultured in the presence of inhibitors with different modes of action. When macrophages were cultured with liposomes and [14C]oleic acid in the presence of triacsin C, a potent inhibitor of long chain acyl-CoA synthetase, both [14C]CE and [14C]TG syntheses were inhibited to similar extents with IC50 values of 0.19 and 0.10 microM, respectively. On the other hand, pregnenolone, a well-known inhibitor of cellular cholesterol transport, and CL-283,546, a potent inhibitor of acyl-CoA:cholesterol acyltransferase, inhibited [14C]CE synthesis specifically with IC50 values of 5.0 and 0.038 microM, respectively. Microscopic observation revealed that the inhibitors of cholesterol metabolism produce only a partial decrease in cytosolic lipid droplets even at the…
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Treating iMGs with triacsin C effectively decreased BODIPY-labelled LDs.
“Treating iMGs with triacsin C (TrC), an inhibitor of long-chain acyl-CoA synthetase that reduces LD formation10,18,19,39,40, effectively decreased BODIPY-labelled LDs (Extended Data Fig. 7e–i).”
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- Authors
- Namatame, I., Tomoda, H., Arai, H., Inoue, K., & Omura, S.
- Affiliations
- Kitasato University (JP)
- The University of Tokyo (JP)
- Venue
- Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-02-01
- Volume
- 125
- Issue
- 2
- Pages
- 319-327
- ISSN
- 0021-924X (ISSN-L)
- OpenAlex
- W2032401910
- Cited by
- 74
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 1 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 2
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- macrophage foam cell formation, lipid droplet formation, cholesteryl ester synthesis, triglyceride synthesis, acyl-CoA, acyl-CoA:cholesterol acyltransferase, peritoneal macrophages, atherosclerosis, neutral lipid synthesis, phosphatidylserine
- MeSH terms
- Long-Chain-Fatty-Acid-CoA Ligase, Animals, Carbon Radioisotopes, Cell Survival, Coenzyme A Ligases, Enzyme Inhibitors, Female, Foam Cells, Lipids, Liposomes, Mice, Inbred ICR, Phosphatidylcholines, Repressor Proteins, Streptomyces, Triazenes, Macrophages, Peritoneal, Oleic Acid, Saccharomyces cerevisiae Proteins, Mice
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