title: The importance of metal ions for the formation and isolation of insulin-like growth factor-binding protein 3-transferrin (IGFBP-3-Tf) complexes, and the analysis of their physiological involvement.
abstract: Insulin-like growth factor (IGF) binding protein 3 (IGFBP-3) is the most abundant IGFBP in the circulation and its main role is to regulate the amount of free, receptor-reactive IGFs that are involved in a broad range of metabolic and mitogenic activities. IGFBP-3 interacts with several other biomolecules forming complexes that might have IGF-dependent or independent functions. Transferrin (Tf) forms complexes with IGFBP-3, but the physiological significance of this interaction remains unclear. Tf is an iron-transporting protein, and is able to carry other metal ions as well. IGFBP-3, on the other hand, possesses one metal-binding domain. As both proteins have the ability to bind metals, the formation of the IGFBP-3-Tf complexes may be expected to influence the metabolism of metal ions and/or mitogenic/metabolic roles in which IGFBP-3 is involved. The aim of this study was to quantify the amount of complexes in the circulation, to investigate the importance of a specific metal ion for their formation and isolation, and to search for the possible physiological place of the IGFBP-3-Tf complexes. The effects of the following ions were analyzed: Fe(3+), Cu(2+), Ni(2+), Mg(2+) and Zn(2+). Results have shown that the amount of IGFBP-3 involved in the complex formation with Tf in healthy persons was 5.4 ± 1.02 nM and iron ions were substantial for their formation and isolation without employment of harsh conditions. The amount of IGFBP-3-Tf complexes was further determined in persons with iron over-load, patients with iron-deficiency anemia and patients with colorectal carcinoma-associated anemia. The amount of complexes was in direct correlation with the concentrations of iron and IGFBP-3. In the case of the colorectal carcinoma-associated anemia, the amount of complexes was inversely correlated with the concentration of ferritin. IGFBP-3, thus, appears to be a member of a network of iron-binding proteins that participates in cell signaling that involves iron-associated response.
authors: Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia. goranm@inep.co.rs
authors: Goran
authors: G
authors: Miljuš
authors: Vesna
authors: V
authors: Malenković
authors: Olgica
authors: O
authors: Nedić
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002846:Chromatography, Affinity; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000737:chemistry*; D008297:Male; D008670:Metals / Q000737:chemistry* / Q000494:pharmacology; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D014168:Transferrin / Q000737:chemistry*; D014462:Ultrafiltration
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D008670:Metals; D014168:Transferrin