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

Abstract

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 0.5 {mu}M 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.
Publication Date:
Dec 12, 2008
Product Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 377; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2008.09.140; PII: S0006-291X(08)01961-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; CHOLESTEROL; COENZYMES; INHIBITION; LIPOPROTEINS; MACROPHAGES
OSTI ID:
21255779
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US09R0112006372
Availability:
Available from http://dx.doi.org/10.1016/j.bbrc.2008.09.140;INIS
Submitting Site:
INIS
Size:
page(s) 484-488
Announcement Date:
Feb 20, 2010

Citation Formats

Rodriguez-Acebes, Sara, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Cueva, Paloma de la, Ferruelo, Antonio J, Fernandez-Hernando, Carlos, Lasuncion, Miguel A, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain), Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain)], Martinez-Botas, Javier, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Gomez-Coronado, Diego, and CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.09.140.
Rodriguez-Acebes, Sara, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Cueva, Paloma de la, Ferruelo, Antonio J, Fernandez-Hernando, Carlos, Lasuncion, Miguel A, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain), Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain)], Martinez-Botas, Javier, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Gomez-Coronado, Diego, & CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation. United States. doi:10.1016/j.bbrc.2008.09.140.
Rodriguez-Acebes, Sara, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Cueva, Paloma de la, Ferruelo, Antonio J, Fernandez-Hernando, Carlos, Lasuncion, Miguel A, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain), Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain)], Martinez-Botas, Javier, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Gomez-Coronado, Diego, and CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es. 2008. "Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation." United States. doi:10.1016/j.bbrc.2008.09.140. https://www.osti.gov/servlets/purl/10.1016/j.bbrc.2008.09.140.
@misc{etde_21255779,
title = {Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation}
author = {Rodriguez-Acebes, Sara, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Cueva, Paloma de la, Ferruelo, Antonio J, Fernandez-Hernando, Carlos, Lasuncion, Miguel A, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain), Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain)], Martinez-Botas, Javier, CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], Gomez-Coronado, Diego, and CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es}
abstractNote = {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 0.5 {mu}M 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.}
doi = {10.1016/j.bbrc.2008.09.140}
journal = {Biochemical and Biophysical Research Communications}
issue = {2}
volume = {377}
place = {United States}
year = {2008}
month = {Dec}
}