Linked Life Data

14752238

Source:http://linkedlifedata.com/resource/pubmed/id/14752238

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-30
pubmed:abstractText
The pathogenesis of glomerular alterations and proteinuria in corticosteroid-responsive nephrotic syndrome (CRNS) is unknown. As an isoform of plasma hemopexin (Hx) with protease activity may be implicated in this disease, we have studied the inhibition of Hx by ADP and reactivation to its active form by endothelial or mesangial cells in vitro. We hypothesized that these cells might potentially be able to convert the inactivated form of Hx (Hxi) to active Hx (Hxa) in vitro, mediated by cellular ecto-ADPase. Since ecto-ADPase (CD39) is upregulated after stimulation of these cells with lipopolysaccharide (LPS) or certain cytokines, we postulated that this conversion might occur specifically after inflammatory stimulation of these cells. Human endothelial or mesangial cell cultures were incubated overnight with or without LPS (10.0 ng/ml) or TNFalpha (10.0 ng/ml), washed and subsequently incubated with Hxi (1.5 mg/ml) in serum-free conditions (Hxi was prepared by treatment of Hxa with ADP or ADP-beta-S). After 60 min, supernatants were tested for their capacity to alter glomerular extracellular matrix molecules (i.e. ecto-apyrase) in vitro using standard methods, and compared with Hxi that had not been incubated with cells. Supernatants containing Hxa (1.5 mg/ml) served as positive control. The results show significant activity in supernatants with Hxi (prepared using native ADP). However, Hxi inactivated by ADP-beta-S (which is non-hydrolyzable) could not be reactivated after contact with LPS-stimulated or unstimulated cells in vitro. As ecto-ADPase of these cells is upregulated by LPS, we believe that reactivation of Hxi to Hxa is mediated by cellular ecto-ADPase. Although the relevance of this inflammation-mediated activation mechanism of Hx in patients with CRNS requires further experimentation, our preliminary observations suggesting that this mechanism is corticosteroid dependent may support a potential role of Hxa in CRNS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1660-2137
pubmed:author
pubmed:copyrightInfo
Copyright 2004 S. Karger AG, Basel
pubmed:issnType
Electronic
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
P1-10
pubmed:dateRevised
2008-4-8
pubmed:meshHeading
pubmed-meshheading:14752238-Adenosine Triphosphatases, pubmed-meshheading:14752238-Animals, pubmed-meshheading:14752238-Antigens, CD, pubmed-meshheading:14752238-Apyrase, pubmed-meshheading:14752238-Cells, Cultured, pubmed-meshheading:14752238-Culture Media, Conditioned, pubmed-meshheading:14752238-Cytokines, pubmed-meshheading:14752238-Endopeptidases, pubmed-meshheading:14752238-Endothelial Cells, pubmed-meshheading:14752238-Glomerular Mesangium, pubmed-meshheading:14752238-Hemopexin, pubmed-meshheading:14752238-Histocytochemistry, pubmed-meshheading:14752238-Humans, pubmed-meshheading:14752238-Kidney Glomerulus, pubmed-meshheading:14752238-Lipopolysaccharides, pubmed-meshheading:14752238-Protease Inhibitors, pubmed-meshheading:14752238-Protein Isoforms, pubmed-meshheading:14752238-Rats, pubmed-meshheading:14752238-Umbilical Veins
pubmed:year
2004
pubmed:articleTitle
Regulation of plasma hemopexin activity by stimulated endothelial or mesangial cells.
pubmed:affiliation
Department of Pathology, University of Groningen, Groningen, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't