Document Detail

Proteoglycan involvement in polyamine uptake.
MedLine Citation:
PMID:  10024506     Owner:  NLM     Status:  MEDLINE    
We have evaluated the possible role of proteoglycans in the uptake of spermine by human lung fibroblasts. Exogenous glycosaminoglycans behaved as competitive inhibitors of spermine uptake, the most efficient being heparan sulphate (Ki=0.16+/-0.04 microM). Treatment of fibroblasts with either heparan sulphate lyase, p-nitrophenyl-O-beta-D-xylopyranoside or chlorate reduced spermine uptake considerably, whereas chondroitin sulphate lyase had a limited effect. Inhibition of polyamine biosynthesis with alpha-difluoromethylornithine resulted in an increase of cell-associated heparan sulphate proteoglycans exhibiting higher affinity for spermine. The data indicate a specific role for heparan sulphate proteoglycans in the uptake of spermine by fibroblasts. Spermine uptake by pgsD-677, a mutant Chinese hamster ovary cell defective in heparan sulphate biosynthesis, was only moderately reduced (20%) compared with wild-type cells. Treatment of mutant cells with the above-mentioned xyloside resulted in a greater reduction of endogenous proteoglycan production as well as a higher inhibition of spermine uptake than in wild-type cells. Moreover, treatment with chondroitin sulphate lyase resulted in a selective inhibition of uptake in mutant cells, indicating a role for chondroitin/dermatan sulphate proteoglycans in the uptake of spermine by these cells. Fibroblasts, made growth-dependent on exogenous spermine by alpha-difluoromethylornithine treatment, were growth-inhibited by heparan sulphate or beta-D-xyloside, which might have future therapeutical implications.
M Belting; S Persson; L A Fransson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  338 ( Pt 2)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-05-06     Completed Date:  1999-05-06     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  317-23     Citation Subset:  IM    
Department of Cell and Molecular Biology, Section of Cell and Matrix Biology, Lund University, P.O. Box 94, S-221 00 Lund, Sweden.
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MeSH Terms
CHO Cells
Cell Division / drug effects
Cell Line
Chlorates / pharmacology
Eflornithine / pharmacology
Glycosides / pharmacology
Heparitin Sulfate / pharmacology
Prostaglandins / biosynthesis
Proteoglycans / metabolism*
Spermine / antagonists & inhibitors,  biosynthesis,  metabolism*
Reg. No./Substance:
0/Chlorates; 0/Glycosides; 0/Prostaglandins; 0/Proteoglycans; 2001-96-9/4-nitrophenyl beta-D-xyloside; 70052-12-9/Eflornithine; 71-44-3/Spermine; 9050-30-0/Heparitin Sulfate

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