Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
48
|
| pubmed:dateCreated |
1998-12-23
|
| pubmed:abstractText |
Shear stress, the dragging force generated by fluid flow, differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in bovine aortic endothelial cells (BAEC) (Jo, H., Sipos, K., Go, Y. M., Law, R., Rong, J., and McDonald, J. M. (1997) J. Biol. Chem. 272, 1395-1401). Here, we examine whether cholesterol-enriched compartments in the plasma membrane are responsible for such differential regulation. Pretreatment of BAEC with a cholesterol-binding antibiotic, filipin, did not inhibit shear-dependent activation of JNK. In contrast, filipin and other membrane-permeable cholesterol-binding agents (digitonin and nystatin), but not the lipid-binding agent xylazine, inhibited shear-dependent activation of ERK. The effect of cholesterol-binding drugs did not appear to be due to membrane permeabilization, since treatment of BAEC with a detergent, Triton X-100 which also permeabilizes membranes, did not inhibit shear-dependent activation of ERK. Furthermore, shear-dependent activation of ERK, but not JNK, was inhibited by cyclodextrin, a membrane-impermeable cholesterol-binding agent, which removes cell-surface cholesterol. Moreover, the effects of cyclodextrin were prevented by adding cholesterol during the incubation. These results indicate that cholesterol or cholesterol-sensitive compartments in the plasma membrane play a selective and essential role in activation of ERK, but not JNK, by shear stress. Although exposure to shear stress (1 h) increased the number of caveolae by 3-fold, treatment with filipin had no effect in either control or shear-exposed cells suggesting that caveolae density per se is not a crucial determinant in shear-dependent ERK activation. In summary, the current study suggests that cholesterol-sensitive microdomains in the plasma membrane, such as caveolae-like domains, play a critical role in differential activation of ERK and JNK by shear stress.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Digitonin,
http://linkedlifedata.com/resource/pubmed/chemical/Filipin,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nystatin,
http://linkedlifedata.com/resource/pubmed/chemical/Xylazine
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
27
|
| pubmed:volume |
273
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
32304-11
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9822710-Animals,
pubmed-meshheading:9822710-Aorta, Thoracic,
pubmed-meshheading:9822710-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9822710-Cattle,
pubmed-meshheading:9822710-Cell Membrane,
pubmed-meshheading:9822710-Cells, Cultured,
pubmed-meshheading:9822710-Cholesterol,
pubmed-meshheading:9822710-Digitonin,
pubmed-meshheading:9822710-Endothelium, Vascular,
pubmed-meshheading:9822710-Enzyme Activation,
pubmed-meshheading:9822710-Filipin,
pubmed-meshheading:9822710-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:9822710-Kinetics,
pubmed-meshheading:9822710-Membrane Lipids,
pubmed-meshheading:9822710-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:9822710-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:9822710-Mitogen-Activated Protein Kinases,
pubmed-meshheading:9822710-Nystatin,
pubmed-meshheading:9822710-Stress, Mechanical,
pubmed-meshheading:9822710-Xylazine
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Plasma membrane cholesterol is a key molecule in shear stress-dependent activation of extracellular signal-regulated kinase.
|
| pubmed:affiliation |
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|