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The effect of lead on iron uptake from transferrin in human erythroleukemia (K562) cells

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Abstract

The effect of lead on cellular iron metabolism has been investigated using human erythroleukemia (K562) cells. When the cells were cultured with 100 μm Pb2+ for 48 h, the rate of cellular iron uptake from transferrin decreased to 46% of that in untreated cells. Scatchard analysis of the binding data revealed that this reduction was the result of a decrease in the number of transferrin receptors rather than an alteration in ligand-receptor affinity. The results of immunoprecipitation of transferrin receptors on the cell surface also confirmed the decreased expression of transferrin receptors by lead-treated cells. The down-regulation of transferrin receptors by treatment with lead did not result from a decrease in the total amount of the receptor, as determined by immunoblotting. Moreover, the biosynthesis of the receptor was unaffected by lead treatment. Thus, the down-regulation of surface transferrin receptors in lead-treated cells might be due to a redistribution of receptors rather than an actual loss of receptors from the cell. Using kinetic analysis, it was shown that redistribution of the receptor did not result from the alteration in the rates of transferrin receptor recycling. A comparison of the amounts of transferrin receptor on the cell surface and in the cycling pool revealed that the sequestration of the receptor from normal flow through the cycle might cause down-regulation of the surface receptor.

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References

  • Albahary C. 1972 Lead and hemopoiesis. The mechanisms and consequences of the erythropathy of occupational lead poisoning. Am J Med 52, 367–378.

    Google Scholar 

  • Bleil JD, Bretscher MS. 1982 Transferrin receptor and its recycling in HeLa cells. EMBO J 1, 351–355.

    Google Scholar 

  • Bomford AB, Munro HN. 1985 Transferrin and its receptor: their roles in cell function. Hepatology 5, 870–875.

    Google Scholar 

  • Bottomley SS, Muller-Eberhard U. 1988 Pathophysiology of heme synthesis. Semin Hematol 25, 282–302.

    Google Scholar 

  • Campbell BC, Brodie MJ, Thompson GG, et al. 1977 Alterations in the activity of enzymes of haem biosynthesis in lead poisoning and acute hepatic porphyia. Clin Sci Mol Med 53, 335–340.

    Google Scholar 

  • Enns CA, Mulkins MA, Sussman H, Root B. 1988 Modulation of the transferrin receptor during DMSO-induced differentiation in HL-60 cells. Exp Cell Res 174, 89–97.

    Google Scholar 

  • Haynes BF, Hemler M, Cotner T, et al. 1981 Characterization of a monoclonal antibody (5E9) that defines a human cell surface antigen of cell activation. J Immunol 127, 347–351.

    Google Scholar 

  • Hunt RC, Ruffin R, Yang Y-S. 1984 Alteration in the transferrin receptor of human erythroleukemic cells after induction of hemoglobin synthesis. J Biol Chem 259, 9944–9952.

    Google Scholar 

  • Hunt RC, Marshall-Carlson L. 1986 Internalization and recycling of transferrin and its receptor. Effect of trifluoperazine on recycling in human erythroleukemic cells. J Biol Chem 261, 3681–3686.

    Google Scholar 

  • Kohno H, Taketani S, Tokunaga R. 1986 Phorbol ester-induced regulation of transferrin receptors in human leukemia K562 cells. Cell Struct Funct 11, 181–190.

    Google Scholar 

  • Laemmli UK. 1970 Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680–685.

    Google Scholar 

  • Lamb JE, Ray F, Ward JH, Kushner JP, Kaplan J. 1983 Internalization and subcellular localization of transferrin receptors in HeLa cells. J Biol Chem 258, 8751–8758.

    Google Scholar 

  • Louache F, Testa U, Pelicci P, et al. 1984 Regulation of transferrin receptors in human hematopoietic cell lines. J Biol Chem 259, 11576–11582.

    Google Scholar 

  • Louache F, Pelosi E. Titeux M, Peschle C, Testa U. 1985 Molecular mechanisms regulating the synthesis of transferrin receptors and ferritin in human erythroleukemic cell lines. FEBS Lett 183, 223–227.

    Google Scholar 

  • Markovac J, Goldstein GW. 1988 Picomolar concentrations of lead stimulate brain protein kinase C. Nature 334, 71–73.

    Google Scholar 

  • May WS, Jacobs S, Cuatrecasas P. 1984 Association of phorbol ester-induced hyperphosphorylation and reversible regulation of transferrin membrane receptor in HL60 cells. Proc Natl Acad Sci USA 81, 2016–2020.

    Google Scholar 

  • Mulford CA, Lodish HF. 1988 Endocytosis of the transferrin receptors is altered during differentiation of murine erythroleukemia cells. J Biol Chem 263, 5455–5461.

    Google Scholar 

  • Pausa CD, Bleil JD, Lennox ES. 1984 The control of transferrin receptor synthesis in mitogen-stimulated human lymphocytes. Exp Cell Res 154, 510–520.

    Google Scholar 

  • Pounds JG. 1984 Effect of lead intoxication on calcium homeostasis and calcium-mediated cell function: a review. Neurotoxicology 5, 295–332.

    Google Scholar 

  • Sawyer ST, Krantz SB. 1986 Transferrin receptor number, synthesis, and endocytosis during erythropoietin-induced maturation of Friend virus-induced erythroid cells. J Biol Chem 261, 9187–9195.

    Google Scholar 

  • Scatchard G. 1949 The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51, 660–675.

    Google Scholar 

  • Simons TJB. 1986 Cellular interactions between lead and calcium. Br Med Bull 42, 431–434.

    Google Scholar 

  • Stein BS, Sussman HH. 1986 Demonstration of two distinct transferrin receptor recycling pathways and transferrin-dependent receptor internalization. J Biol Chem 261, 10319–10331.

    Google Scholar 

  • Taketani S, Kohno H, Tokunaga R. 1985 Expression and phosphorylation of transferrin receptors in mitogen-activated peripheral blood lymphocytes. J Biochem 98, 1639–1646.

    Google Scholar 

  • Taketani S, Kohno H, Naitoh Y, Tokunaga R. 1987 Isolation of the hemopexin receptor from human placenta. J Biol Chem 262, 8668–8671.

    Google Scholar 

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Kohno, H., Taketani, S. & Tokunaga, R. The effect of lead on iron uptake from transferrin in human erythroleukemia (K562) cells. Biometals 6, 77–83 (1993). https://doi.org/10.1007/BF00140107

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