Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases
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Iveta Dobreva
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-β-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.
References
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©2005 by Walter de Gruyter Berlin New York
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- Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases
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- Inhibition of cathepsin B reduces β-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate β-secretase of Alzheimer's disease
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Artikel in diesem Heft
- Paper of the Year 2004: Award to Yin Wang and Iris Lorenzi
- Improving the levels of essential amino acids and sulfur metabolites in plants
- Symmetry at the active site of the ribosome: structural and functional implications
- GPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways
- Developing an effective RNA interference strategy against a plus-strand RNA virus: silencing of coxsackievirus B3 and its cognate coxsackievirus-adenovirus receptor
- NF-κB contributes to transcription of placenta growth factor and interacts with metal responsive transcription factor-1 in hypoxic human cells
- Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP
- Role of the N-terminal region and of β-sheet residue Thr29 on the activity of the ω2 global regulator from the broad-host range Streptococcus pyogenes plasmid pSM19035
- Lysine 3 acetylation regulates the phosphorylation of yeast 6-phosphofructo-2-kinase under hypo-osmotic stress
- Determination of the specificity of monoclonal antibodies against Schistosoma mansoni CAA glycoprotein antigen using neoglycoconjugate variants
- Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases
- Focal adhesion kinase is redistributed to focal complexes and mediates cell spreading in macrophages in response to M-CSF
- Inhibition of cathepsin B reduces β-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate β-secretase of Alzheimer's disease
- Activation processing of cathepsin H impairs recognition by its propeptide
