Characterization of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) interaction with the Bovine Aortic Endothelial (BAE) cell surface: Examination of the Role of Heparan Sulfate Proteoglycans (HSPG)

Insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the insulin-like growth factor (IGF-I). However, their precise role is as yet unclear. Further, recent studies have indicated that IGFBP-3 has a receptor mediated growth inhibitory response of its own. In the present study, we quantified the binding characteristics of IGFBP-3 to bovine aortic endothelial (BAE) cells. Binding studies at 4 ^oC were conducted and a specific binding curve for IGFBP-3 was obtained. IGFBP-3 was found to bind with an equilibrium dissociation constant (K_D) value of 3.1 x 10^-10 M. The role of heparan sulfate proteoglycans (HSPG) in the IGFBP-3 binding mechanism was also examined. It was seen that inactivation of the cell surface HSPGs with 75 mM sodium chlorate did not affect IGFBP-3 binding. Further, there have been reports of inhibition of IGFBP-3 binding by heparin in the media. Hence, the most probable interaction of HSPG with IGFBP-3 occurs in the extracellular region, with soluble HSPGs acting as receptors for IGFBP-3 and decreasing the net cell associated ligand receptor interaction. This is likely, since IGFBP-3 is known to possess a heparin binding domain. Simultaneous introduction of IGF-I and IGFBP-3 into the extracellular media decreased IGFBP-3 binding to the cell surface, which might imply that IGF-I and IGFBP-3 regulate each other's action.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Chemical Engineering

Department dc:contributor.department

Chemical Engineering

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1998

Author dc:creator

• Parghi, Nirav

Chair dc:contributor.committeechair

• Forsten-Williams, Kimberly

Committee members dc:contributor.committeemember

• Conger, William L.
• Akers, Robert Michael

• KD
• HSPG
• IGFBP-3
• binding
• BAE

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-72398-15376

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/36928