In vivo and in vitro iron deficiency reduces protein kinase C activity and translocation in murine splenic and purified T cells.
We investigated the effects of iron deficiency anemia, iron repletion, and iron chelation by deferoxamine on protein kinase C (PKC) activity, an enzyme that plays a crucial role on T lymphocyte proliferation. The study involved 23 control (C), 18 pairfed (PF), and 24 iron deficient (ID) mice or ID mice that were repleted for 3 (n = 14), 7 (n = 17), or 14 (n = 14) days. The low iron (0.09 mmol iron/kg) and iron-supplemented (0.9 mmol iron/kg) diets were fed to mice for 53 days. Mean hemoglobin, hematocrit, and liver iron stores of ID mice were one third of those of C mice. Lymphocyte proliferation was reduced (P < 0.05) in spleen and purified T cells in ID but not PF mice. In concanavalin A, phytohemagglutinin, and anti-CD3 antibody-treated and untreated cells that were incubated in serum-free and serum-containing medium, PKC activity was significantly (P < 0.05) reduced in ID but not PF mice and returned to normal before correction of anemia. In mitogen-treated cells, while the ratios of membrane-bound to cytosol activity increased nearly seven-fold (from 0.4-0.63 in resting cells to 1.43-7.23) in spleen cells from C, PF, and repleted mice and 11-fold in T cells (P < 0.005), they remained below 1 in ID mice suggesting reduced translocation. In vitro iron chelation by deferoxamine for 120 min prior to cell activation reduced (P < 0.05) PKC activity by 46-60% in C and PF and 28-53% in ID mice. The data suggest that: 1) it is iron-deficiency but not anemia or differences in the proportion of immunocompetent T cells that reduced PKC activity in cells from ID mice; 2) reduced PKC translocation may play an important role on altered lymphocyte proliferation and associated functions in iron-deficient individuals.
Kuvibidila
S R
SR
Department of Pediatrics, Division of Hematology/Oncology, Louisiana State University School of Medicine, New Orleans, Louisiana 70112, USA.solok@mail.peds.lsumc.edu
Kitchens
D
D
Baliga
B S
BS
D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000494:pharmacology / Q000502:physiology*; D019266:Iron, Dietary / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000201:enzymology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D017252:CD3 Complex; D002614:Chelating Agents; D016895:Culture Media, Serum-Free; D006454:Hemoglobins; D019266:Iron, Dietary; D008934:Mitogens; D010835:Phytohemagglutinins; D003208:Concanavalin A; D007501:Iron; D011493:Protein Kinase C; D003676:Deferoxamine