Document Detail


Effect of oversulfated chondroitin-6-sulfate or oversulfated fucoidan in the activation of glutamic plasminogen by tissue plasminogen activator: role of lysine and cyanogen bromide-fibrinogen.
MedLine Citation:
PMID:  18180617     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fucoidan and chondroitin-6-sulfate were oversulfated using chlorosulfonic acid-pyridine complex and were isolated as the sodium salt. Infrared analysis of oversulfated compounds showed introduction of sulfate groups in new positions, and in-vitro studies of the compounds showed a significant increase in the anticoagulant property. Addition of 28.6 microg/ml oversulfated compound gave a two-fold to four-fold increase in the rate of enhancement of activation of glutamic plasminogen by tissue plasminogen activator using 0.05 mol/l Tris buffer (pH 7.35) containing physiological concentrations of NaCl (0.9%). Under these conditions, unfractionated heparin was not active and the native compounds gave less than 30% enhancement. In the present study, the effect of lysine or cyanogen bromide-treated fibrinogen, alone or in combination with the oversulfated compounds, on the activation of glutamic plasminogen by tissue plasminogen activator was investigated. Addition of 16.2 mmol/l L-lysine gave three-fold to four-fold enhancement of activation, which was further enhanced to five-fold to six-fold by addition of 2.86 microg/ml oversulfated chondroitin-6-sulfate or oversulfated fucoidan. Cyanogen bromide-treated fibrinogen (50 microg/ml) gave a 10-fold enhancement of activation by itself, and addition of 2.86 microg/ml oversulfated compounds amplified this to 15-fold. A 25-fold to 35-fold enhancement of activation of glutamic plasminogen was obtained when 2.86 microg/ml oversulfated compounds were combined with 16.2 mmol/l lysine and 50 microg/ml cyanogen bromide-treated fibrinogen. Dilution studies showed that the amplification of the enhancement of lysine by 2.86 microg/ml oversulfated compound was related to interaction of the cofactors with both glutamic plasminogen and tissue plasminogen activator.
Authors:
Yaneth E Carranza; Dorian Anderson; Vasant Doctor
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis     Volume:  19     ISSN:  0957-5235     ISO Abbreviation:  Blood Coagul. Fibrinolysis     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-08     Completed Date:  2008-03-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9102551     Medline TA:  Blood Coagul Fibrinolysis     Country:  England    
Other Details:
Languages:  eng     Pagination:  60-5     Citation Subset:  IM    
Affiliation:
Chemistry Department, Prairie View A&M University, Texas 77445, USA.
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MeSH Terms
Descriptor/Qualifier:
Chondroitin Sulfates / chemistry,  pharmacology*
Cyanogen Bromide / chemistry,  pharmacology
Drug Interactions
Fibrinogen / chemistry,  physiology
Humans
Lysine / pharmacology*
Plasminogen / drug effects*,  physiology
Polysaccharides / chemistry,  pharmacology*
Protein Binding
Structure-Activity Relationship
Sulfates / chemistry
Tissue Plasminogen Activator / drug effects,  metabolism
Grant Support
ID/Acronym/Agency:
08094//PHS HHS
Chemical
Reg. No./Substance:
0/Polysaccharides; 0/Sulfates; 506-68-3/Cyanogen Bromide; 56-87-1/Lysine; 9001-32-5/Fibrinogen; 9001-91-6/Plasminogen; 9007-28-7/Chondroitin Sulfates; 9072-19-9/fucoidan; EC 3.4.21.68/Tissue Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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