Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages
The mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant that governs its availability for efflux to extracellular acceptors. NPC1 and NPC2 are proteins localized in the late endosome and control cholesterol transport from the lysosome to the plasma membrane....
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doaj-57df255bdb9a4c368dcc184243fe66122021-04-27T04:43:24ZengElsevierJournal of Lipid Research0022-22752005-12-01461227172725Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophagesG. Chinetti-Gbaguidi0E. Rigamonti1L. Helin2A.L. Mutka3M. Lepore4J.C. Fruchart5V. Clavey6E. Ikonen7S. Lestavel8B. Staels9UR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceUR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceUR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceInstitute of Biotechnology, University of Helsinki, Helsinki, FinlandUR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceUR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceUR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceInstitute of Biotechnology, University of Helsinki, Helsinki, FinlandUR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceTo whom correspondence should be addressed.; UR 545 Inserm, Institut Pasteur de Lille and Université de Lille 2, Lille, FranceThe mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant that governs its availability for efflux to extracellular acceptors. NPC1 and NPC2 are proteins localized in the late endosome and control cholesterol transport from the lysosome to the plasma membrane. Here, we report that NPC1 and NPC2 gene expression is induced by oxidized LDL (OxLDL) in human macrophages. Because OxLDLs contain natural activators of peroxisome proliferator-activated receptor α (PPARα), a fatty acid-activated nuclear receptor, the regulation of NPC1 and NPC2 by PPARα and the consequences on cholesterol trafficking were further studied. NPC1 and NPC2 expression is induced by synthetic PPARα ligands in human macrophages. Furthermore, PPARα activation leads to an enrichment of cholesterol in the plasma membrane. By contrast, incubation with progesterone, which blocks postlysosomal cholesterol trafficking, as well as NPC1 and NPC2 mRNA depletion using small interfering RNA, abolished ABCA1-dependent cholesterol efflux induced by PPARα activators.These observations identify a novel regulatory role for PPARα in the control of cholesterol availability for efflux that, associated with its ability to inhibit cholesterol esterification and to stimulate ABCA1 and scavenger receptor class B type I expression, may contribute to the stimulation of reverse cholesterol transport.http://www.sciencedirect.com/science/article/pii/S0022227520328601nuclear receptorsgene regulationatherosclerosischolesterol homeostasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
G. Chinetti-Gbaguidi E. Rigamonti L. Helin A.L. Mutka M. Lepore J.C. Fruchart V. Clavey E. Ikonen S. Lestavel B. Staels |
spellingShingle |
G. Chinetti-Gbaguidi E. Rigamonti L. Helin A.L. Mutka M. Lepore J.C. Fruchart V. Clavey E. Ikonen S. Lestavel B. Staels Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages Journal of Lipid Research nuclear receptors gene regulation atherosclerosis cholesterol homeostasis |
author_facet |
G. Chinetti-Gbaguidi E. Rigamonti L. Helin A.L. Mutka M. Lepore J.C. Fruchart V. Clavey E. Ikonen S. Lestavel B. Staels |
author_sort |
G. Chinetti-Gbaguidi |
title |
Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages |
title_short |
Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages |
title_full |
Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages |
title_fullStr |
Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages |
title_full_unstemmed |
Peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages |
title_sort |
peroxisome proliferator-activated receptor α controls cellular cholesterol trafficking in macrophages |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2005-12-01 |
description |
The mobilization of cholesterol from intracellular pools to the plasma membrane is a determinant that governs its availability for efflux to extracellular acceptors. NPC1 and NPC2 are proteins localized in the late endosome and control cholesterol transport from the lysosome to the plasma membrane. Here, we report that NPC1 and NPC2 gene expression is induced by oxidized LDL (OxLDL) in human macrophages. Because OxLDLs contain natural activators of peroxisome proliferator-activated receptor α (PPARα), a fatty acid-activated nuclear receptor, the regulation of NPC1 and NPC2 by PPARα and the consequences on cholesterol trafficking were further studied. NPC1 and NPC2 expression is induced by synthetic PPARα ligands in human macrophages. Furthermore, PPARα activation leads to an enrichment of cholesterol in the plasma membrane. By contrast, incubation with progesterone, which blocks postlysosomal cholesterol trafficking, as well as NPC1 and NPC2 mRNA depletion using small interfering RNA, abolished ABCA1-dependent cholesterol efflux induced by PPARα activators.These observations identify a novel regulatory role for PPARα in the control of cholesterol availability for efflux that, associated with its ability to inhibit cholesterol esterification and to stimulate ABCA1 and scavenger receptor class B type I expression, may contribute to the stimulation of reverse cholesterol transport. |
topic |
nuclear receptors gene regulation atherosclerosis cholesterol homeostasis |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520328601 |
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