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Titolo:
In vivo involvement of heparan sulfate proteoglycan in the bioavailability, internalization, and catabolism of exogenous basic fibroblast growth factor
Autore:
Colin, S; Jeanny, JC; Mascarelli, F; Vienet, R; Al-Mahmood, S; Courtois, Y; Labarre, J;
Indirizzi:
Hop Tarnier Cochin, Lab Oncol, F-75006 Paris, France Hop Tarnier Cochin Paris France F-75006 Lab Oncol, F-75006 Paris, France CEA Saclay, Serv Biochim & Genet Mol, F-91191 Gif Sur Yvette, France CEA Saclay Gif Sur Yvette France F-91191 F-91191 Gif Sur Yvette, France Assoc Claude Bernard, CNRS, INSERM U450, Paris, France Assoc Claude Bernard Paris France ard, CNRS, INSERM U450, Paris, France CEA Saclay, Serv Pharmacol & Immunol, F-91191 Gif Sur Yvette, France CEA Saclay Gif Sur Yvette France F-91191 F-91191 Gif Sur Yvette, France
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 1, volume: 55, anno: 1999,
pagine: 74 - 82
SICI:
0026-895X(199901)55:1<74:IVIOHS>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PLASMINOGEN-ACTIVATOR PRODUCTION; CAPILLARY ENDOTHELIAL-CELLS; EXTRACELLULAR-MATRIX; IN-VITRO; PROTEOLYTIC DEGRADATION; FACTOR RECEPTOR; FGF RECEPTORS; BINDING; AFFINITY; GLOMERULONEPHRITIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Colin, S Hop Tarnier Cochin, Lab Oncol, 89 Rue Assas, F-75006 Paris, France Hop Tarnier Cochin 89 Rue Assas Paris France F-75006 ris, France
Citazione:
S. Colin et al., "In vivo involvement of heparan sulfate proteoglycan in the bioavailability, internalization, and catabolism of exogenous basic fibroblast growth factor", MOLEC PHARM, 55(1), 1999, pp. 74-82

Abstract

The in vivo bioavailability of exogenous fibroblast growth factor 2 (FGF2)was studied after i.v. injection of uniformly C-14-labeled FGF2 into youngrats. C-14-FGF2 was rapidly accumulated in almost all solid organs within 5 min. After 30 min, more than 65% of FGF2 was retained in liver, 4.5% in kidneys, 1.2% in spleen, 0.15% in adrenal glands, and trace amounts in bone marrow, eyes, lungs,and heart. Suborgan distribution of C-14-FGF2 showed that for kidneys and adrenal glands, the labeling was mainly concentrated in the cortical zone. Incubation of organ sections with 2 M NaCl or heparin eluted all the radioactivity, indicating that labeling was due to FGF2-heparan sulfate proteoglycan (HSPG) interactions. Electrophoretic analysis show only native C-14-FGF2 in the blood and extracellular matrix; however, FGF2 is continuously catabolized in solid organs, indicating that all participatein the clearance of FGF2 by cellular internalization and subsequent catabolism. All FGF2 catabolic fragments bound heparin, demonstrating the preservation of their HSPG-binding site during the in vivo intracellular catabolism of FGF2. Analysis of the high-affinity receptors of FGF2 (FGFR-1 and FGFR-3) and the mitogen-activated protein kinase did not show any increase in either FGFR tyrosine phosphorylation or in mitogen-activated protein kinase activation. This study shows for the first time that exogenous FGF2 is cleaved by HSPG cellular internalization and catabolism without inducing the activation of FGFRs within at least five organs in vivo, which strongly suggests that the HSPG-dependent internalization and catabolism pathway may control the in vivo bioavailability of FGF2.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 16:59:22