Linked Life Data

15104238

Source:http://linkedlifedata.com/resource/pubmed/id/15104238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-4-23
pubmed:abstractText
Endothelial barrier dysfunction plays a pivotal role in the pathogenesis of diabetic vascular complications. Although recent studies have established a link between protein kinase C (PKC) pathway and hyperglycaemic-induced vascular permeability, it is unclear which PKC isoforms involve increased endothelial cell permeability. In the present study, we investigated whether high glucose induced endothelial hyperpermeability via distinct PKC isoforms in human umbilical vein endothelial cells (HUVECs) and whether increased endothelial permeability could be substantially reversed by PKC inhibitors LY379196 and hypocrellin A (HA). High glucose (20 mM) and phorbol-myristate-acetate (PMA)-induced endothelial hyperpermeability was almost abolished by 150 nM HA and partially reduced by 30 nM PKC beta inhibitor (LY379196). LY379196 and HA inhibited the membrane fraction of PKC activity in a dose-dependent manner. Western blot analysis revealed high-glucose-induced overexpression of PKC alpha and PKC beta2 in the membrane fraction of HUVECs. LY379196 (30 and 150 nM) selectively inhibited PKC beta2 with no significant effect on PKC alpha expression. HA (150 nM) significantly reduced PKC alpha expression with no inhibitory effect on PKC beta2. At higher concentrations (300 nM), both LY379196 and HA were no longer selective for PKC beta or alpha, respectively. This study showed that both PKC alpha and beta2 contributed to endothelial hyperpermeability. Since reduction of endothelial hyperpermeability was greater with inhibition of PKC alpha rather than PKC beta2, we conclude that PKC alpha may be a major isoform involved in endothelial permeability in HUVECs, and that PKC alpha-mediated endothelial permeability was significantly reversed by the PKC inhibitor HA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
855-64
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Reduction of high glucose and phorbol-myristate-acetate-induced endothelial cell permeability by protein kinase C inhibitors LY379196 and hypocrellin A.
pubmed:affiliation
Department of Health Sciences, University of Technology, Sydney, P.O. Box 123, Broadway, NSW 2007, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't