Zinc Partitions Insulin-Like Growth Factors (IGFs) from Soluble IGF Binding Protein (IGFBP)-5 to the Cell Surface Receptors of BC3H-1 Muscle Cells

Robert H. McCusker, Jan E Novakofski

Research output: Contribution to journalArticle

Abstract

Zinc (Zn2+) is a multifunctional micronutrient. The list of functions for this micronutrient expanded with the recent discovery that Zn 2+ retains insulin-like growth factors binding proteins (IGFBPs) on the surface of cultured cells, lowers the affinity of cell-associated IGFBPs, and increases the affinity of the cell surface insulin-like growth factor (IGF)-type 1 receptor (IGF-1R). However, currently there is no information concerning the effect of Zn2+ on soluble IGFBPS. In the current study, the soluble IGFBP-5 secreted by BC3H-1 cells is shown to bind approximately 50% more [125I]-IGF-II than [125I]-IGF-I at pH 7.4. Zn2+ is shown to depress the binding of both IGF-I and IGF-II to soluble secreted IGFBP-5; [125I]-IGF-I binding is affected more so than [125I]-IGF-II binding. Zn2+ acts by lowering the affinity (Ka) of IGFBP-5 for the IGFs. Scatchard plots are non-linear indicating the presence of high and low affinity binding sites; Zn2+ affects only binding to the high affinity site. In contrast, Zn2+ increases the affinity by which either [125I]-IGF-I or [125I]-R3-IGF-I binds to the IGF-1R, but depresses [125I]-IGF-II binding to the IGF-type 2 receptor (IGF-2R) on BC 3H-1 cells. By depressing the association of the IGFs with soluble IGFBPs, Zn2+ is shown to repartition either [125I]-IGF-I or [125I]-IGF-II from soluble IGFBP-5 onto cell surface IGF receptors. Zn2+ was active at physiological doses depressing IGF binding to IGFBP-5 and the IGF-2R at 15-20 μM. Hence, a novel mechanism is further characterized by which the trace micronutrient Zn2+ could regulate IGF activity.

Original languageEnglish (US)
Pages (from-to)388-399
Number of pages12
JournalJournal of Cellular Physiology
Volume197
Issue number3
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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