Linked Life Data

7817829

Source:http://linkedlifedata.com/resource/pubmed/id/7817829

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1995-2-6
pubmed:abstractText
Synthetic Arg-Gly-Asp (RGD)-containing peptides were examined in bone resorption or attachment and detachment assays with isolated mammalian osteoclasts in an effort to elucidate the mechanistic and structural basis for the inhibition of bone resorption by s-echistatin. Bone resorption was the process most sensitive to inhibition by s-echistatin, with IC50 = 0.3 nM; inhibition of attachment to bone or detachment (lamellipodial retraction) was 30- to 70-fold less sensitive, with IC50 = 10 or 20 nM, respectively. Single amino acid substitutions within the 49-residue sequence of s-echistatin showed that although the efficacy of s-echistatin is dependent on the Arg24-Gly25-Asp26 sequence, additional residues, including Asp27, Met28, and Cys39, are also critical for potent inhibition of the resorbing activity of isolated rat osteoclasts. Because of the identification of the av beta 3 as the primary integrin on rat osteoclasts interacting the RGD peptides (Helfrich et al.), we examined the possibility of modeling bone resorption with other beta 3-mediated processes. Specifically, av beta 3 endothelial cell (human or rat) attachment to vitronectin and aIIb beta 3 platelet aggregation were compared with bone resorption for sensitivity to s-echistatin analogs, linear RGD peptides, and cyclic RGD peptides. Essentially no similarity in sensitivity to RGD peptides were observed between bone resorption, platelet aggregation, or endothelial cell attachment. Because rat osteoclasts and human giant cell tumors (osteoclastomas) shared similar sensitivity to s-echistatin and rat and human endothelial cells showed a similar sensitivity profile to RGD peptides, the dissimilarity of bone resorption to other beta 3-mediated processes cannot be explained in terms of species differences.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0884-0431
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1441-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7817829-Amino Acid Sequence, pubmed-meshheading:7817829-Animals, pubmed-meshheading:7817829-Bone Neoplasms, pubmed-meshheading:7817829-Bone Resorption, pubmed-meshheading:7817829-Cell Adhesion, pubmed-meshheading:7817829-Cells, Cultured, pubmed-meshheading:7817829-Dose-Response Relationship, Drug, pubmed-meshheading:7817829-Endothelium, Vascular, pubmed-meshheading:7817829-Female, pubmed-meshheading:7817829-Giant Cell Tumor of Bone, pubmed-meshheading:7817829-Humans, pubmed-meshheading:7817829-Mice, pubmed-meshheading:7817829-Microscopy, Confocal, pubmed-meshheading:7817829-Microscopy, Electron, Scanning, pubmed-meshheading:7817829-Microscopy, Fluorescence, pubmed-meshheading:7817829-Molecular Sequence Data, pubmed-meshheading:7817829-Oligopeptides, pubmed-meshheading:7817829-Organ Culture Techniques, pubmed-meshheading:7817829-Osteoclasts, pubmed-meshheading:7817829-Peptides, pubmed-meshheading:7817829-Platelet Aggregation, pubmed-meshheading:7817829-Platelet Aggregation Inhibitors, pubmed-meshheading:7817829-Rats, pubmed-meshheading:7817829-Rats, Sprague-Dawley, pubmed-meshheading:7817829-Structure-Activity Relationship, pubmed-meshheading:7817829-Viper Venoms
pubmed:year
1994
pubmed:articleTitle
Structure-activity studies of the s-echistatin inhibition of bone resorption.
pubmed:affiliation
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.