Linked Life Data

10709911

Source:http://linkedlifedata.com/resource/pubmed/id/10709911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-4-24
pubmed:abstractText
The effects and possible role of heparin on tissue plasminogen activator-mediated plasminogen activation was thoroughly investigated. Direct analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that heparin increased the conversion of plasminogen to plasmin. Experiments by fluorescence quenching suggested that the stimulation of tissue plasminogen activator activity probably was due to a direct binding of heparin to tissue plasminogen activator, causing a conformational change of tissue plasminogen activator and rendering it more accessible to plasminogen interaction. The absence of additive stimulation effects on tissue plasminogen activator-mediated plasminogen activation when both heparin and fibrinogen were present also implied that both compounds interacted with tissue plasminogen activator via the same domain; it appeared to be most likely via the kringle-2 domain in tissue plasminogen activator based on studies using epsilon-aminocaproic acid as an inhibitor. Unlike heparin-induced stimulation of antithrombin-thrombin interaction, the heparin-induced stimulation of tissue plasminogen activator did not seem to follow a template model. Only in the presence of a high plasminogen or a low tissue plasminogen activator concentration, massive stimulation of tissue plasminogen activator activity was observed via a pseudotemplate model. The results suggest that precautions concerning high heparin dose should be given during its conjunctive clinical use with tissue plasminogen activator in thrombolytic therapy to reduce the risk of hemorrhage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0049-3848
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
349-58
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10709911-Binding Sites, pubmed-meshheading:10709911-Chromogenic Compounds, pubmed-meshheading:10709911-Dextran Sulfate, pubmed-meshheading:10709911-Dose-Response Relationship, Drug, pubmed-meshheading:10709911-Enzyme Activation, pubmed-meshheading:10709911-Fibrinogen, pubmed-meshheading:10709911-Heparin, pubmed-meshheading:10709911-Humans, pubmed-meshheading:10709911-Kinetics, pubmed-meshheading:10709911-Lipoproteins, pubmed-meshheading:10709911-Oligopeptides, pubmed-meshheading:10709911-Osmolar Concentration, pubmed-meshheading:10709911-Plasminogen, pubmed-meshheading:10709911-Protein Binding, pubmed-meshheading:10709911-Protein Conformation, pubmed-meshheading:10709911-Spectrometry, Fluorescence, pubmed-meshheading:10709911-Sulfates, pubmed-meshheading:10709911-Tissue Plasminogen Activator
pubmed:year
2000
pubmed:articleTitle
The potential mechanism for the effect of heparin on tissue plasminogen activator-mediated plasminogen activation.
pubmed:affiliation
College of Pharmacy, The University of Michigan, Ann Arbor 48109-1065, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't