Linked Life Data

21621512

Source:http://linkedlifedata.com/resource/pubmed/id/21621512

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-6-20
pubmed:abstractText
Uremic toxins such as indoxyl sulfate (IS) accumulate at a high level in end stage renal disease (ESRD) and can exhibit significant systemic endothelial toxicity leading to accelerated cardiovascular events. The precise molecular mechanisms by which IS causes endothelial dysfunction are unknown. We tested the hypothesis that IS negatively influences properties of endothelial cells, such as migration and tube formation, by depleting nitric oxide (NO) bioavailability, and that an NO donor can reverse these inhibitory effects. IS inhibited human umbilical vein endothelial cell (HUVEC) migration and formation of tubes on matrigel. Mechanistically, IS inhibited VEGF-induced NO release from HUVECs. An NO donor, SNAP, reversed IS-mediated inhibition of HUVEC migration as well as tube-formation. IS inhibited ERK 1/2 MAP kinase activity in a dose-dependent manner, but this was preserved by SNAP. Inhibition of ERK 1/2 with a pharmacological inhibitor (U0126) decreased HUVEC migration and tube formation; these effects too were prevented by SNAP. Further, IS stimulated activation of myosin light chain (MLC), potentially stimulating endothelial contractility, while SNAP decreased MLC activation. Thus, we conclude that the negative effects of IS on endothelial cells are prevented, to a major extent, by NO, via its divergent actions on ERK MAP kinase and MLC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
409
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
758-63
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Nitric oxide counters the inhibitory effects of uremic toxin indoxyl sulfate on endothelial cells by governing ERK MAP kinase and myosin light chain activation.
pubmed:affiliation
Division of Nephrology, University of California, San Francisco, CA 94143, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural