Linked Life Data

15064242

Source:http://linkedlifedata.com/resource/pubmed/id/15064242

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-4-5
pubmed:abstractText
We used a two-compartment coculture model comprising human endothelial cells (EC) and non-small cell lung carcinoma (CA) cells to study capillary formation. Elevated NO concentrations, contributed in part by CA cells, lead to inhibited capillary formation (Phillips PG, Birnby LM, Narendran A, and Milonovich WL. Am J Physiol Lung Cell Mol Physiol 281: L278-L290, 2001). Here we demonstrate using gelatin substrate zymography that high NO concentrations, whether produced endogenously or by NO donor spermine-NONOate or peroxynitrite-generating compound SIN-1, significantly inhibit MMP-9 expression and activation. Furthermore, high NO concentrations decrease Cav-1 abundance and alter its cellular distribution in EC. Cav-1 is essential for capillary formation in this model because Cav-1 antisense treatments targeted to EC significantly inhibit capillary formation. Laser confocal microscopy demonstrated extensive colocalization of MMP-9 with Cav-1 in sprouting EC, primarily at the basolateral surfaces of EC in focal structures associated with directed migration. This codistribution was NO concentration dependent, and elevated NO concentrations lead to marked dissociation of these two proteins. We propose that compartmentalization of MMP-9 within caveolar structures does occur, and that this could facilitate directed proteolysis essential for early migratory and invasive processes. Our data suggest elevated NO concentrations could impact on capillary formation via a combination of direct effects on MMP activation and by altering the distribution or abundance of Cav-1. Consequences of Cav-1 alterations may include impaired activation of proteolytic enzymes that utilize caveolar structure for stabilization and/or compartmentalization of MMP-9 as well as other putative members of an ECM proteolytic cascade.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L1055-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Nitric oxide modulates caveolin-1 and matrix metalloproteinase-9 expression and distribution at the endothelial cell/tumor cell interface.
pubmed:affiliation
Research Service, Samuel S. Stratton VA Medical Center, 113 Holland Ave., Albany, NY 12208, USA. Patricia.Phillips3@med.va.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.