| Caveolae are an essential component of the pathway for endothelial cell signaling associated with abrupt reduction of shear stress. | |
| | |
MedLine Citation:
|
PMID: 18573285 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Abrupt cessation of flow representing the acute loss of shear stress (simulated ischemia) to flow-adapted pulmonary microvascular endothelial cells (PMVEC) leads to reactive oxygen species (ROS) generation that signals for EC proliferation. We evaluated the role of caveolin-1 on this cellular response with mouse PMVEC that were preconditioned for 72 h to laminar flow at 5 dyn/cm(2) followed by stop of flow ("ischemia"). Preconditioning resulted in a 2.7-fold increase in cellular expression of K(ATP) (K(IR) 6.2) channels but no change in expression level of caveolin-1, gp91(phox), or MAP kinases. The initial response to ischemia in wild type cells was cell membrane depolarization that was abolished by gene targeting of K(IR) 6.2. The subsequent response was increased ROS production associated with activation of NADPH oxidase (NOX2) and then phosphorylation of MAP kinases (Erk, JNK). After 24 h of ischemia in wild type cells, the cell proliferation index increased 2.5 fold and the % of cells in S+G(2)/M phases increased 6-fold. This signaling cascade (cell membrane depolarization, ROS production, MAP kinase activation and cell proliferation) was abrogated in caveolin-1 null PMVEC or by treatment of wild type cells with filipin. These studies indicate that caveolin-1 functions as a shear sensor in flow-adapted EC resulting in ROS-mediated cell signaling and endothelial cell proliferation following the abrupt reduction in flow. |
| | |
Authors:
|
Tatyana Milovanova; Shampa Chatterjee; Brian J Hawkins; Nankang Hong; Elena M Sorokina; Kris Debolt; Jonni S Moore; Muniswamy Madesh; Aron B Fisher |
Related Documents
:
|
12598535 - Hydrogen peroxide formation and actin filament reorganization by cdc42 are essential fo... 15377495 - Important role for rac1 in regulating reactive oxygen species generation and pulmonary ... 2680385 - Cytochrome p-450, reductive metabolism, and cell injury. 6781425 - Improved oxygen delivery to the myocardium during hypothermia by perfusion with 2,3 dpg... 16015095 - Effects of cryopreservation on histology and viability of cultured corneal epithelial c... 10614655 - Leptin and leptin receptor expression in rat and mouse pituitary cells. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-05-23 |
Journal Detail:
|
Title: Biochimica et biophysica acta Volume: 1783 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2008 Oct |
Date Detail:
|
Created Date: 2008-09-09 Completed Date: 2008-11-13 Revised Date: 2011-03-10 |
Medline Journal Info:
|
Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 1866-75 Citation Subset: IM |
Affiliation:
|
Institute For Environmental Medicine, University of Pennsylvania Medical Center, One John Morgan Building, Philadelphia, PA 19104-6068, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adaptation, Physiological Animals Caveolae / metabolism* Caveolin 1 / deficiency, genetics, metabolism Cell Membrane / metabolism Cells, Cultured Endothelial Cells / metabolism* Ischemia / genetics, metabolism* Mice Mice, Inbred C57BL Mice, Knockout Mitogen-Activated Protein Kinases / metabolism Phenotype Phosphorylation Reactive Oxygen Species / metabolism Signal Transduction* Stress, Mechanical |
| Grant Support | |
ID/Acronym/Agency:
|
HL75587/HL/NHLBI NIH HHS; P50 HL060290-040002/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Caveolin 1; 0/Reactive Oxygen Species; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Overexpression of functional TrkA receptors after internalisation in human airway smooth muscle cell...
Next Document: Rapid fluorescent assay for screening drugs on Leishmania amastigotes.