Zinc partitions IGFs from soluble IGF binding proteins (IGFBP)-5, but not soluble IGFBP-4, to myoblast IGF type 1 receptors

R. H. McCusker, J. Novakofski

Research output: Contribution to journalArticle

Abstract

Zinc (Zn2+), a multifunctional micronutrient, was recently shown to lower the affinity of cell-associated insulin-like growth factor (IGF) binding protein (IGFBP)-3 and IGFBP-5 for both IGF-I and IGF-II, but to increase the affinity of the cell surface type 1 IGF receptor (IG-1R) for the same two ligands. However, there is a need for data concerning the effects of Zn 2+ on soluble IGFBPs and the type 2 IGF receptor (IGF-2R). In the current work, we demonstrate that Zn2+ affects the affinity of IGFBP-5 secreted by myoblasts but not IGFBP-4. Zn2+, at physiological levels, depressed binding of both IGF-I and IGF-II to IGFBP-5, affecting 125I-IGF-II more than 125I-IGF-II. Both 125I-IGF-I and 125I-IGF-II bound to high and low affinity sites on IGFBP-5. Zn2+ converted the high affinity binding sites of IGFBP-5 into low affinity binding sites. An IGF-I analog, 125I-R3-IGF-I, did not bind to the soluble murine IGFBP-5. Zn 2+ also decreased the affinity of the IGF-2R on L6 myoblasts. In contrast, Zn2+ increased IGF-I, IGF-II and R3-IGF-I binding to the IGF-1R by increasing ligand binding affinity on both P2A2a-LISN and L6 myoblasts. Soluble IGFBP-5 and I-IGFBP-4 depressed the binding of 125I-IGF-I and 125I-IGF-II to the IGF-1R, but did not affect binding of 125I-R3-IGF-I. By depressing the association of the IGFs with soluble IGFBP-5, Zn2+ partitioned 125I-IGF-I and 125I-IGF-II from soluble IGFBP-5 onto cell surface IGF-1Rs. This effect is not seen when soluble L6-derived IGFBP-4 is present in extracellular fluids. We introduce a novel mechanism by which the trace micronutrient Zn2+ may alter IGF distribution, i.e. Zn2+ acts to increase IGF-1R binding at the expense of IGF binding to soluble IGFBP-5 and the IGF-2R.

Original languageEnglish (US)
Pages (from-to)227-246
Number of pages20
JournalJournal of Endocrinology
Volume180
Issue number2
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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