title: The inability of cells to grow in low iron correlates with increasing activity of their iron regulatory protein (IRP).
abstract: We studied the factors that determine the differing growth requirements of low-iron-tolerant (LIT) versus high-iron-dependent (HID) cells for extracellular nontransferrin iron. The growth of LIT cells HeLa and THP-1, when transferred from transferrin (5 micrograms/ml) medium into low-iron (5 microM ferric citrate) medium, was not significantly affected while HID cells Jiyoye and K562 showed nearly no growth. HeLa and THP-1 cells, as well as Jiyoye and K562 cells, do not produce transferrin in sufficient amounts to support their growth in low-iron medium. Surprisingly, similar rates of iron uptake in low-iron medium (0.033 and 0.032 nmol Fe/min and 10(6) cells) were found for LIT cells HeLa and HID cells K562. Furthermore, the intracellular iron level (4.64 nmol/10(6) cells) of HeLa cells grown in low-iron medium was much higher than iron levels (0.15 or 0.20 nmol/10(6) cells) of HeLa or K562 cells grown in transferrin medium. We demonstrated that the activity (ratio activated/total) of the iron regulatory protein (IRP) in HID cells Jiyoye and K562 increased more than twofold (from 0.32 to 0.79 and from 0.47 to 1.12, respectively) within 48 h after their transfer into low-iron medium. In the case of LIT cells HeLa and THP-1, IRP activity stayed at similar or slightly decreased levels (0.86-0.73 and 0.58-0.55, respectively). Addition of iron chelator deferoxamine (50 microM, i.e., about half-maximal growth-inhibitory dose) resulted in significantly increased activity of IRP also in HeLa and THP-1 cells. We hypothesize that the relatively higher bioavailability of nontransferrin iron in LIT cells, over that in HID cells, determines the differing responses observed under low-iron conditions.
authors.affiliation: Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kovár
authors.forename: L C
authors.initials: LC
authors.lastname: Kühn
authors.forename: V
authors.initials: V
authors.lastname: Richardson
authors.forename: C
authors.initials: C
authors.lastname: Seiser
authors.forename: K
authors.initials: K
authors.lastname: Kriegerbecková
authors.forename: J
authors.initials: J
authors.lastname: Musílková
mesh_terms: D001692:Biological Transport; D002051:Burkitt Lymphoma; D002455:Cell Division; D003470:Culture Media; D003676:Deferoxamine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D007948:Leukemia, Monocytic, Acute; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014168:Transferrin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D014168:Transferrin; D007501:Iron; D003676:Deferoxamine