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Titolo:
DIFFERENT EFFECTS OF MUCOSAL, BOVINE LUNG AND CHEMICALLY-MODIFIED HEPARIN ON SELECTED BIOLOGICAL PROPERTIES OF BASIC FIBROBLAST GROWTH-FACTOR
Autore:
COLTRINI D; RUSNATI M; ZOPPETTI G; ORESTE P; GRAZIOLI G; NAGGI A; PRESTA M;
Indirizzi:
UNIV BRESCIA,SCH MED,DEPT BIOMED SCI & BIOTECHNOL,GEN PATHOL & IMMUNOL UNIT I-25123 BRESCIA ITALY UNIV BRESCIA,SCH MED,DEPT BIOMED SCI & BIOTECHNOL,GEN PATHOL & IMMUNOL UNIT I-25123 BRESCIA ITALY ITALFARMACO SPA,RES CTR I-20092 CINISELLO BALSAMO ITALY G RONZONI INST CHEM & BIOCHEM I-20133 MILAN ITALY
Titolo Testata:
Biochemical journal
, volume: 303, anno: 1994,
parte:, 2
pagine: 583 - 590
SICI:
0264-6021(1994)303:<583:DEOMBL>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL-CELL GROWTH; PROTEOLYTIC DEGRADATION; 3-DIMENSIONAL STRUCTURE; HIGH-AFFINITY; BINDING; SULFATE; RECEPTOR; FGF; IDENTIFICATION; SEQUENCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
D. Coltrini et al., "DIFFERENT EFFECTS OF MUCOSAL, BOVINE LUNG AND CHEMICALLY-MODIFIED HEPARIN ON SELECTED BIOLOGICAL PROPERTIES OF BASIC FIBROBLAST GROWTH-FACTOR", Biochemical journal, 303, 1994, pp. 583-590

Abstract

Heparins from bovine mucosa and lung, and chemically modified heparins were assayed for their capacity to: (i) protect human recombinant basic fibroblast growth factor (bFGF) from tryptic cleavage; (ii) prevent I-125-bFGF binding to heparan sulphate proteoglycans present in the extracellular matrix and on the eel surface of fetal bovine aortic endothelial GM 7373 cell cultures, (iii) affect I-125-bFGF binding to high-affinity tyrosine kinase FGF receptors present on the cell membrane of GM 7373 cells; (iv) inhibit the mitogenic activity exerted by bFGF in the same cells. The results demonstrate that the potency shown by mucosal heparins in the different assays is a direct function of size, very-low-molecular-mass heparin (2.0 kDa) being significantly less effective on a molar basis than unfractionated heparin (13.6 kDa). Increased flexibility of the backbone structure, as observed in reduced/oxidized heparins of different size, does not affect the capacity of the polysaccharide to interact with bFGF. In contrast, selective 2-O-desulphation, but not 6-O-desulphation, drastically reduced the capacity of heparin to protect bFGF from proteolytic cleavage, to affect its interaction with low- and high-affinity sites, and to inhibit its mitogenicactivity. Two preparations of bovine lung heparin, differing in molecular mass, were as effective as mucosal heparin in the bFGF-tryptic-digestion assay and the endothelial-cell proteoglycan-binding assay, butthey were highly inefficient at inhibiting the capacity of bFGF to interact with its tyrosine kinase receptors. Bovine lung heparins were also less effective than mucosal heparin as bFGF antagonists in GM 7373-cell-proliferation assays. N-Desulphated/N-acetylated bovine lung heparin retained only a significant capacity to protect bFGF from trypticcleavage. The results demonstrate that different chemical features ofthe heparin molecule, including decrease in molecular mass, selectivedesulphation, disaccharide composition and clustering, affect differently the capacity of the glycosaminoglycan to interact with bFGF and to influence its biological behaviour in different assays in vitro and in endothelial cell cultures. Our findings should aid the design of synthetic oligosaccharides aimed at improving the,bioavailability of bFGF when administered in vivo as a therapeutic agent.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 16:59:28