Basic fibroblast growth factor-heparan sulphate complex in the human dialysis-related amyloidosis

1995 ◽  
Vol 427 (4) ◽  
Author(s):  
H. Morita ◽  
T. Shinzato ◽  
Z. Cai ◽  
K. Maeda ◽  
M. Ito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Heparan Sulphate ◽  
Fibroblast Growth

scholarly journals Heparin and heparan sulphate protect basic fibroblast growth factor from non-enzymic glycosylation

1999 ◽  
Vol 338 (3) ◽  
pp. 637 ◽  
Author(s):  
Nicholas N. NISSEN ◽  
Ravi SHANKAR ◽  
Richard L. GAMELLI ◽  
Ashok SINGH ◽  
Luisa A. DIPIETRO
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Heparan Sulphate ◽  
Fibroblast Growth

scholarly journals Basic fibroblast growth factor does not prevent heparan sulphate proteoglycan catabolism in intact cells, but it alters the distribution of the glycosaminoglycan degradation products

1999 ◽  
Vol 337 (3) ◽  
pp. 471-481 ◽  
Author(s):  
Sarka TUMOVA ◽  
Brian A. HATCH ◽  
Douglas J. LAW ◽  
Karen J. BAME
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Cho Cells ◽  
Degradation Products ◽  
Biological Activities ◽  
Heparan Sulphate ◽  
Primary Role ◽  
Fibroblast Growth ◽  
Intact Cells

Heparan sulphate proteoglycans on cell surfaces have been shown to mediate the degradation or recycling of several ligands. Since the interaction with ligand may affect proteoglycan catabolism once the complex is internalized, this could alter the cellular pool of heparan sulphate chains, with possible consequences for heparan sulphate-mediated cellular processes. We have recently demonstrated that the specific binding of basic fibroblast growth factor (bFGF) to heparan sulphate chains prevents the glycosaminoglycan from being degraded by partially purified heparanases from Chinese hamster ovary (CHO) cells [Tumova and Bame (1997) J. Biol. Chem. 272, 9078–9085]. The present study examines the effect of bFGF on heparan sulphate catabolism in intact cells. The distribution and size of the heparan sulphate degradation products in CHO cells was analysed in the presence and absence of bFGF using pulse–chase protocols. Although heparan sulphate molecules and bFGF are internalized through the same pathway, even relatively high concentrations of the growth factor do not have any inhibitory effects on glycosaminoglycan degradation. However, the interaction with the growth factor alters the distribution of heparan sulphate-degradation products, presumably by preventing secretion of the short heparanase-derived species. Our findings show that most of the free and bFGF-bound heparan sulphate chains are destined for lysosomes, which would be consistent with a recent hypothesis that the primary role of proteoglycan-mediated internalization of the growth factor is to remove bFGF from its site of action at the cell surface. However, in the presence of bFGF, a fraction of intracellular, heparanase-degraded heparan sulphate chains is delivered to the nucleus, suggesting that the glycosaminoglycan accompanies the growth factor to the organelle. It may be important for bFGF activity that the growth factor is protected from proteolytic degradation by its interaction with heparan sulphate. This work demonstrates that the internalization of a ligand along with the proteoglycan can affect the sorting of heparan sulphate-degradation products in endosomes, and the ultimate destination of the short glycosaminoglycan. It also provides evidence that formation of heparan sulphate–ligand complexes may regulate the recycling and degradation of both ligands and heparan sulphate chains and, consequently, affect their biological activities.

scholarly journals Structure of a heparan sulphate oligosaccharide that binds to basic fibroblast growth factor

1992 ◽  
Vol 285 (3) ◽  
pp. 805-813 ◽  
Author(s):  
H Habuchi ◽  
S Suzuki ◽  
T Saito ◽  
T Tamura ◽  
T Harada ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Culture Medium ◽  
Specific Binding ◽  
Heparan Sulphate ◽  
Fibroblast Growth ◽  
Exogenous Addition ◽  
Limited Digestion ◽  
Unsaturated Disaccharide

Binding of basic fibroblast growth factor (bFGF) to the extracellular matrix of cultured bovine aorta smooth muscle cells is likely to be mediated via heparan sulphate, since not only exogenous addition of heparan sulphate to the culture medium but also pretreatment of the cells with heparitinase (but not chondroitinase ABC) resulted in loss of binding. Comparison of the affinity of bFGF to various glycosaminoglycan-conjugated gels showed a direct and specific binding of bFGF to heparan sulphate. Heparan sulphate also bound to a bFGF affinity gel. However, the proportion of heparan sulphate bound varied depending on the source of the HS (more than 90% and 45% with pig aorta heparan sulphate and mouse EHS tumour heparan sulphate respectively). The bound heparan sulphate had the ability to protect bFGF from proteolytic digestion, but the unbound heparan sulphate did not. The results suggest the presence in the bound heparan sulphate of a specific structure involved in binding. Limited digestion with heparitinase I of porcine aorta heparan sulphate yielded 13% oligosaccharides bound to the gel, of which the smallest were octasaccharides. Analysis of a hexadecasaccharide fraction which was obtained at the highest yield among the bound oligosaccharides was performed by h.p.l.c. of the deamination products obtained with nitrous acid and the unsaturated disaccharide products formed by heparitinase digestion. Comparison of the disaccharide unit compositions exhibited a marked difference in IdoA(2SO4)GlcNSO3 and IdoA(2SO4)GlcNSO3(6SO4) units between the bound and unbound hexadecasaccharides. The amounts measured were 3 mol and 1 mol per mol of the former and 0.4 mol and 0.6 mol per mol of the latter. It is likely that the binding of bFGF to heparan sulphate may require the domain structure of the heparan sulphate to be composed of clustering IdoA(2SO4)-GlcNSO3 units.

scholarly journals Expression of basic fibroblast growth factor in intact and ulcerated human gastric mucosa

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 525-536 ◽  
Author(s):  
M A Hull ◽  
J L Brough ◽  
D G Powe ◽  
G I Carter ◽  
D Jenkins ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gastric Mucosa ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Heparan Sulphate ◽  
Gastric Ulcers ◽  
Human Gastric Mucosa ◽  
Antral Mucosa ◽  
Fibroblast Growth ◽  
Heparan Sulphate Proteoglycans

Background—Basic fibroblast growth factor (bFGF) promotes angiogenesis and healing of gastric ulcers in rats, and bFGF expression is up regulated in such ulcers. However, little is known about expression of bFGF in human gastric mucosa.Aims—To investigate bFGF expression in intact human gastric mucosa and gastric ulcers and to determine whether low bFGF content or altered binding by mucosa is associated with ulceration.Subjects—Endoscopy outpatients, gastrectomy patients, and organ donors.Methods—bFGF was isolated by heparin affinity chromatography and characterised by western blotting and endothelial cell bioassay. bFGF was measured by immunoassay and its distribution defined by immunohistochemistry and in situ hybridisation. Binding of bFGF by heparan sulphate proteoglycans was investigated by sodium chloride and heparin extraction.Results—Bioactive bFGF (19 kDa) was detected in normal mucosa but bFGF mRNA was not found. bFGF expression was up regulated in granulation tissue endothelial cells, mononuclear cells, and epithelial cells at the ulcer rim. Gastric ulcer patients had constitutively low bFGF concentrations in intact antral mucosa which were not explained by changes in binding to heparan sulphate proteoglycans.Conclusions—bFGF expression is up regulated in human gastric ulcers. Low intact mucosal bFGF content is associated with gastric ulceration.

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