Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases.

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Version: Final published version
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Serval ID
serval:BIB_AD05CBB84366
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases.
Journal
Biological chemistry
Author(s)
Dobreva I., Zschörnig O., Waeber G., James R.W., Widmann C.
ISSN
1431-6730
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
386
Number
9
Pages
909-18
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
Elevated low-density lipoprotein (LDL) levels induce activation of the p38 mitogen-activated protein kinase (MAPK), a stress-activated protein kinase potentially participating in the development of atherosclerosis. The nature of the lipoprotein components inducing p38 MAPK activation has remained unclear however. We show here that both LDLs and high-density lipoproteins (HDLs) have the ability to stimulate the p38 MAPKs with potencies that correlate with their cholesterol content. Cholesterol solubilized in methyl-beta-cyclodextrin was sufficient to activate the p38 MAPK pathway. Liposomes made of phosphatidylcholine (PC) or sphingomyelin, the two main phospholipids found in lipoproteins, were unable to stimulate the p38 MAPKs. In contrast, PC liposomes loaded with cholesterol potently activated this pathway. Reducing the cholesterol content of LDL particles lowered their ability to activate the p38 MAPKs. Cell lines representative of the three main cell types found in blood vessels (endothelial cells, smooth muscle cells and fibroblasts) all activated their p38 MAPK pathway in response to LDLs or cholesterol-loaded PC liposomes. These results indicate that elevated cholesterol content in lipoproteins, as seen in hypercholesterolemia, favors the activation of the stress-activated p38 MAPK pathway in cells from the vessel wall, an event that might contribute to the development of atherosclerosis.
Keywords
Animals, Cells, Cultured, Cholesterol, Endothelial Cells, Enzyme Activation, Humans, Kinetics, Lipoproteins, LDL, Liposomes, Muscle, Smooth, Rats, Signal Transduction, p38 Mitogen-Activated Protein Kinases
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 14:43
Last modification date
14/02/2022 7:56
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