Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5μM lovastatin and lipoprotein-deficient serum suppressed cell prolife...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-12, Vol.377 (2), p.484-488
Main Authors: Rodríguez-Acebes, Sara, Cueva, Paloma de la, Ferruelo, Antonio J., Fernández-Hernando, Carlos, Lasunción, Miguel A., Martínez-Botas, Javier, Gómez-Coronado, Diego
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Acetylated LDL
Animals
Cell Line
CELL PROLIFERATION
Cell Proliferation - drug effects
CHOLESTEROL
Cholesterol, LDL - pharmacology
COENZYMES
Desmosterol
Desmosterol - pharmacology
Dose-Response Relationship, Drug
Hydroxymethyl glutaryl coenzyme A reductase
INHIBITION
LIPOPROTEINS
Lovastatin
Macrophage proliferation
MACROPHAGES
Macrophages - cytology
Macrophages - drug effects
Mevalonate
Mice
Native LDL
Oxidized LDL
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Summary:We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5μM lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.09.140