title: Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.
abstract: One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.
authors: Department of Nutrition, University of California, Davis, California 95616-8669, USA.
authors: Brad J
authors: BJ
authors: Niles
authors: Michael S
authors: MS
authors: Clegg
authors: Lynn A
authors: LA
authors: Hanna
authors: Susan S
authors: SS
authors: Chou
authors: Tony Y
authors: TY
authors: Momma
authors: Heeok
authors: H
authors: Hong
authors: Carl L
authors: CL
authors: Keen
mesh_terms: D016475:3T3 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001052:Apoferritins / Q000096:biosynthesis; D001205:Ascorbic Acid / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000096:biosynthesis; D035942:Iron Regulatory Protein 2 / Q000096:biosynthesis; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D020218:Response Elements / Q000502:physiology; D015032:Zinc / Q000172:deficiency*
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D009569:Nitric Oxide; D001052:Apoferritins; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D015032:Zinc; D001205:Ascorbic Acid; D000111:Acetylcysteine