Linked Life Data

11238665

Source:http://linkedlifedata.com/resource/pubmed/id/11238665

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-3-12
pubmed:abstractText
Complement plays a significant role in mediating endothelial injury following oxidative stress. We have previously demonstrated that the lectin complement pathway (LCP), which is initiated by deposition of the mannose-binding lectin (MBL), is largely responsible for activating complement on endothelial cells following periods of oxidative stress. Identifying functional inhibitors that block MBL binding will be useful in characterizing the role of the LCP in disease models. The human cytokeratin peptide SFGSGFGGGY has been identified as a molecular mimic of N-acetyl-D-glucosamine (GlcNAc), a known ligand of MBL. Thus, we hypothesized that this peptide would specifically bind to MBL and functionally inhibit the LCP on endothelial cells following oxidative stress. Using a BIAcore 3000 optical biosensor, competition experiments were performed to demonstrate that the peptide SFGSGFGGGY inhibits binding of purified recombinant human MBL to GlcNAc in a concentration-dependent manner. Solution affinity data generated by BIAcore indicate this peptide binds to MBL with an affinity (K(D)) of 5 x 10(-5) mol/L. Pretreatment of human serum (30%) with the GlcNAc-mimicking peptide (10-50 microg/ml) significantly attenuated MBL and C3 deposition on human endothelial cells subjected to oxidative stress in a dose-dependent manner, as demonstrated by cell surface ELISA and confocal microscopy. Additionally, this decapeptide sequence attenuated complement-dependent VCAM-1 expression following oxidative stress. These data indicate that a short peptide sequence that mimics GlcNAc can specifically bind to MBL and functionally inhibit the proinflammatory action of the LCP on oxidatively stressed endothelial cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4148-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11238665-Acetylglucosamine, pubmed-meshheading:11238665-Binding, Competitive, pubmed-meshheading:11238665-Carrier Proteins, pubmed-meshheading:11238665-Cell Line, pubmed-meshheading:11238665-Cells, Cultured, pubmed-meshheading:11238665-Collectins, pubmed-meshheading:11238665-Complement Activation, pubmed-meshheading:11238665-Complement C3, pubmed-meshheading:11238665-Endothelium, Vascular, pubmed-meshheading:11238665-Humans, pubmed-meshheading:11238665-Immunosuppressive Agents, pubmed-meshheading:11238665-Keratins, pubmed-meshheading:11238665-Lectins, pubmed-meshheading:11238665-Mannans, pubmed-meshheading:11238665-Molecular Mimicry, pubmed-meshheading:11238665-Oxidative Stress, pubmed-meshheading:11238665-Peptide Fragments, pubmed-meshheading:11238665-Recombinant Proteins, pubmed-meshheading:11238665-Surface Plasmon Resonance, pubmed-meshheading:11238665-Transfection
pubmed:year
2001
pubmed:articleTitle
A keratin peptide inhibits mannose-binding lectin.
pubmed:affiliation
Department of Anesthesiology, Perioperative and Pain Medicine, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't