McCusker Robert H, Novakofski Jan
Department of Animal Sciences, Laboratory for Developmental Endocrinology, The University of Illinois, Urbana, Illinois 61801, USA.
J Cell Physiol. 2003 Dec;197(3):388-99. doi: 10.1002/jcp.10360.
Zinc (Zn(2+)) 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 Zn(2+) on soluble IGFBPs. In the current study, the soluble IGFBP-5 secreted by BC(3)H-1 cells is shown to bind approximately 50% more [(125)I]-IGF-II than [(125)I]-IGF-I at pH 7.4. Zn(2+) is shown to depress the binding of both IGF-I and IGF-II to soluble secreted IGFBP-5; [(125)I]-IGF-I binding is affected more so than [(125)I]-IGF-II binding. Zn(2+) acts by lowering the affinity (K(a)) of IGFBP-5 for the IGFs. Scatchard plots are non-linear indicating the presence of high and low affinity binding sites; Zn(2+) affects only binding to the high affinity site. In contrast, Zn(2+) increases the affinity by which either [(125)I]-IGF-I or [(125)I]-R(3)-IGF-I binds to the IGF-1R, but depresses [(125)I]-IGF-II binding to the IGF-type 2 receptor (IGF-2R) on BC(3)H-1 cells. By depressing the association of the IGFs with soluble IGFBPs, Zn(2+) is shown to repartition either [(125)I]-IGF-I or [(125)I]-IGF-II from soluble IGFBP-5 onto cell surface IGF receptors. Zn(2+) was active at physiological doses depressing IGF binding to IGFBP-5 and the IGF-2R at 15-20 microM. Hence, a novel mechanism is further characterized by which the trace micronutrient Zn(2+) could regulate IGF activity.
锌（Zn(2+)）是一种多功能的微量营养素。随着最近发现Zn(2+)能使胰岛素样生长因子结合蛋白（IGFBPs）保留在培养细胞表面，降低细胞相关IGFBPs的亲和力，并增加细胞表面胰岛素样生长因子（IGF）-1型受体（IGF-1R）的亲和力，这种微量营养素的功能列表得以扩展。然而，目前尚无关于Zn(2+)对可溶性IGFBPs影响的信息。在本研究中，BC(3)H-1细胞分泌的可溶性IGFBP-5在pH 7.4时与[(125)I]-IGF-II的结合量比与[(125)I]-IGF-I的结合量多约50%。结果表明，Zn(2+)可抑制IGF-I和IGF-II与可溶性分泌型IGFBP-5的结合；[(125)I]-IGF-I的结合受影响程度大于[(125)I]-IGF-II的结合。Zn(2+)通过降低IGFBP-5对IGFs的亲和力（K(a)）起作用。Scatchard图呈非线性，表明存在高亲和力和低亲和力结合位点；Zn(2+)仅影响与高亲和力位点的结合。相反，Zn(2+)增加[(125)I]-IGF-I或[(125)I]-R(3)-IGF-I与IGF-1R的结合亲和力，但降低[(125)I]-IGF-II与BC(3)H-1细胞上IGF-2型受体（IGF-2R）的结合。通过抑制IGFs与可溶性IGFBPs的结合，Zn(2+)可使[(125)I]-IGF-I或[(125)I]-IGF-II从可溶性IGFBP-5重新分配到细胞表面IGF受体上。Zn(2+)在生理剂量下（15 - 20 microM）具有活性，可抑制IGF与IGFBP-5和IGF-2R的结合。因此，一种新的机制得以进一步阐明，即微量营养素Zn(2+)可通过该机制调节IGF活性。
