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 µM). Treatment of fibroblasts with either heparan sulphate lyase, p-nitrophenyl-O-β-d-xylopyranoside or chlorate reduced spermine uptake considerably, whereas chondroitin sulphate lyase had a limited effect. Inhibition of polyamine biosynthesis with α-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 α-difluoromethylornithine treatment, were growth-inhibited by heparan sulphate or β-d-xyloside, which might have future therapeutical implications.
Skip Nav Destination
Research Article| February 22 1999
Proteoglycan involvement in polyamine uptake
Mattias BELTING 1
1Department of Cell and Molecular Biology, Section of Cell and Matrix Biology, Lund University, P. O. Box 94, S-221 00 Lund, Sweden
1To whom correspondence should be addressed (e-mail Mattias.Belting@medkem.lu.se).
Search for other works by this author on:
Mattias BELTING, Susanne PERSSON, Lars-Åke FRANSSON; Proteoglycan involvement in polyamine uptake. Biochem J 1 March 1999; 338 (2): 317–323. doi: https://doi.org/10.1042/bj3380317
Download citation file:
Don't already have an account? Register
Get Access To This Article
Buy This Article