Document Detail


Neutralizing the anticoagulant activity of ultra-low-molecular-weight heparins using N-acetylglucosamine 6-sulfatase.
MedLine Citation:
PMID:  23374371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heparin has been the most commonly used anticoagulant drug for nearly a century. The drug heparin is generally categorized into three forms according to its molecular weight: unfractionated (UF, average molecular weight 13 000), low molecular weight (average molecular weight 5000) and ultra-low-molecular-weight heparin (ULMWH, average molecular weight 2000). An overdose of heparin may lead to very dangerous bleeding in patients. Protamine sulfate may be administered as an antidote to reverse heparin's anticoagulant effect. However, there is no effective antidote for ULMWH. In the current study, we examine the use of human N-acetylglucosamine 6-sulfatase (NG6S), expressed in Chinese hamster ovary cells, as a reversal agent for ULMWH. NG6S removes a single 6-O-sulfo group at the non-reducing end of the ULMWH Arixtra(®) (fondaparinux), effectively removing its ability to bind to antithrombin and preventing its inhibition of coagulation factor Xa. These results pave the way to developing human NG6S as an antidote for neutralizing the anticoagulant activity of ULMWHs.
Authors:
Xianxuan Zhou; Lingyun Li; Robert J Linhardt; Jian Liu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-06
Journal Detail:
Title:  The FEBS journal     Volume:  280     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-10     Completed Date:  2013-07-02     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  2523-32     Citation Subset:  IM    
Copyright Information:
© 2013 The Authors Journal compilation © 2013 FEBS.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anticoagulants / chemistry
Antidotes / chemistry
Binding Sites
Blotting, Western
CHO Cells
Chromatography, High Pressure Liquid
Cricetinae
Enzyme Activation
Heparin Antagonists / chemistry*
Heparin, Low-Molecular-Weight / antagonists & inhibitors*,  chemistry
Humans
Molecular Weight
Plasmids / chemistry
Polysaccharides / chemistry
Sulfatases / chemistry*,  genetics,  pharmacology
Time Factors
Transfection
Grant Support
ID/Acronym/Agency:
HL094463/HL/NHLBI NIH HHS; HL096972/HL/NHLBI NIH HHS; R01 GM038060/GM/NIGMS NIH HHS; R01 HL062244/HL/NHLBI NIH HHS; R01 HL094463/HL/NHLBI NIH HHS; R01 HL096972/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Antidotes; 0/Heparin Antagonists; 0/Heparin, Low-Molecular-Weight; 0/Polysaccharides; EC 3.1.6.-/Sulfatases; EC 3.1.6.14/N-acetylglucosamine-6-sulfatase; J177FOW5JL/fondaparinux
Comments/Corrections

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


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