Heparin protects heparin-binding growth factor-I from proteolytic inactivation in vitro.
Heparin inhibits proteolytic digestion of heparin-binding growth factor-I (HBGF-I) by trypsin, plasmin and other proteases. This property is lost after thermal denaturation of HBGF-I, suggesting that a heparin:HBGF-I structural interaction rather than a heparin:trypsin interaction is responsible for the resistance of HBGF-I to digestion with trypsin. Heparin is also able to partially protect HBGF-I from thermal denaturation as demonstrated by the ability of heparin to protect HBGF-I from trypsin digestion. The protective effect of heparin is dependent upon the concentration of heparin as well as temperature and duration of denaturation. Autoradiography of 125I-HBGF-I incubated with human umbilical vein endothelial cells demonstrates near complete protection of HBGF-I from proteolytic modification when the incubation is performed in the presence of heparin. These data suggest that (i) the mechanism of the heparin-induced increase in human endothelial cell number at confluence involves the protection of HBGF-I by heparin against proteolytic inactivation and (ii) heparin provides conformational stability to the proteolytic growth factor which reduces the susceptibility of HBGF-I to denaturation.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D016220:Fibroblast Growth Factor 1; D006133:Growth Substances / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism*
D006133:Growth Substances; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D010447:Peptide Hydrolases