The biosynthesis of anticoagulant heparan sulfate by the heparan sulfate 3-O-sulfotransferase isoform 5

被引：33

作者：

Duncan, MB

Chen, JH

Krise, JP

Liu, J

机构：

[1] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2004年 / 1671卷 / 1-3期

关键词：

heparan sulfate; antithrombin; anticoagulation; heparan sulfate sulfotransferase; blood coagulation;

D O I：

10.1016/j.bbagen.2003.12.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The role of heparan sulfate (HS) in regulating blood coagulation has a wide range of clinical implications. In this study, we investigated the role of 3-O-sulfotransferase isoform 5 (3-OST-5) in generating anticoagulant HS in vivo. A Chinese hamster ovary cell line (3OST5/CHO) stably expressing 3-OST-5 was generated. The expression of 3-OST-5 in 3OST5/CHO cells was confirmed by Northern blot analysis, RT-PCR, and the disaccharide analyses of the HS from the cells. We also determined the effects of the HS from 3OST5/CHO on antithrombin-mediated inhibition of factor Xa. Fluorescently labeled antithrombin bound to the surface of 3OST5/CHO cells, suggesting that the antithrombin-binding HS is indeed present on the cell surface. Our results demonstrate that the 3-OST-5 gene is capable of synthesizing anticoagulant HS in CHO cells and has the potential to contribute to the biosynthesis of anticoagulant HS in humans. (C) 2004 Elsevier B.V. All rights reserved.

引用

页码：34 / 43

页数：10

共 31 条

[11] ANALYSIS OF AFFINITY AND STRUCTURAL SELECTIVITY IN THE BINDING OF PROTEINS TO GLYCOSAMINOGLYCANS - DEVELOPMENT OF A SENSITIVE ELECTROPHORETIC APPROACH [J].