LIP - Labile Iron Pool

Labile iron pool is also known as 'free' iron or NTBI - non transferrin bound iron or NPBI - non protein bound iron

(HOME) Blood 1988 Oct;72(4):1416-9

Nontransferrin-bound iron in plasma from hemochromatosis patients: effect of phlebotomy therapy.

Aruoma OI, Bomford A, Polson RJ, Halliwell B

Department of Biochemistry, University of London, United Kingdom.

Plasma from patients with iron overload resulting from idiopathic hemochromatosis contains nontransferrin-bound iron, measurable by the bleomycin, assay. During venesection therapy, the concentration of bleomycin iron declines in a way highly correlated with plasma ferritin concentrations. Even when patients had been venesected to give very low total plasma iron concentrations and high transferrin iron-binding capacity, bleomycin-detectable iron was still present at low concentrations. Bleomycin-detectable iron can stimulate damaging free radical reactions, and its persistence in plasma even after prolonged venesection might contribute to the tissue damage that results from iron overload.

PMID: 2458783, UI: 89001210

Blood 2000 May 1;95(9):2960-6

Intracellular iron status as a hallmark of mammalian cell susceptibility to oxidative stress: a study of L5178Y mouse lymphoma cell lines differentially sensitive to H(2)O(2).

Lipinski P, Drapier JC, Oliveira L, Retmanska H, Sochanowicz B, Kruszewski M

Department of Molecular Biology, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland. lipinkskip@rocketmail.com

The redox properties of iron make this metal a key participant in oxygen-mediated toxicity. Accordingly, L5178Y (LY) mouse lymphoma cell lines, which display a unique inverse cross-sensitivity to ionizing radiation (IR) and hydrogen peroxide (H(2)O(2)), are a suitable model for the study of possible differences in the constitutive control of intracellular iron availability. We report here that the level of iron in the cytosolic labile iron pool (LIP), ie, potentially active in the Fenton reaction, is more than 3-fold higher in IR-resistant, H(2)O(2)-sensitive (LY-R) cells than in IR-sensitive, H(2)O(2)-resistant (LY-S) cells. This difference is associated with markedly greater content of ferritin H-subunits (H-Ft) in LY-S than in LY-R cells. Our results show that different expression of H-Ft in LY cells is a consequence of an up-regulation of H-Ft mRNA in the LY-S mutant cell line. In contrast, posttranscriptional control of iron metabolism mediated by iron-responsive element-iron regulatory proteins (IRPs) interaction is similar in the 2 cell lines, although IRP1 protein levels in iron-rich LY-R cells are twice those in iron-deficient LY-S cells. In showing that LY cell lines exhibit 2 different patterns of intracellular iron regulation, our results highlight both the role of high LIP in the establishment of pro-oxidant status in mammalian cells and the antioxidant role of ferritin. (Blood. 2000;95:2960-2966)

PMID: 10779446, UI: 20243325

Blood 2001 May 1;97(9):2863-71

Repression of ferritin expression increases the labile iron pool, oxidative stress, and short-term growth of human erythroleukemia cells.

Kakhlon O, Gruenbaum Y, Cabantchik ZI

Departments of Biological Chemistry and of Genetics, Institute of Life Sciences, Hebrew University, Jerusalem, Israel.

[Medline record in process]

The role of ferritin expression on the labile iron pool of cells and its implications for the control of cell proliferation were assessed. Antisense oligodeoxynucleotides were used as tools for modulating the expression of heavy and light ferritin subunits of K562 cells. mRNA and protein levels of each subunit were markedly reduced by 2-day treatment with antisense probes against the respective subunit. Although the combined action of antisense probes against both subunits reduced their protein expression, antisense repression of one subunit led to an increased protein expression of the other. Antisense treatment led to a rise in the steady-state labile iron pool, a rise in the production of reactive oxygen species after pro-oxidative challenges and in protein oxidation, and the down-regulation of transferrin receptors. When compared to the repression of individual subunits, co-repression of each subunit evoked a more than additive increase in the labile iron pool and the extent of protein oxidation. These treatments had no detectable effects on the long-term growth of cells. However, repression of ferritin synthesis facilitated the renewal of growth and the proliferation of cells pre-arrested at the G(1)/S phase. Renewed cell growth was significantly less dependent on external iron supply when ferritin synthesis was repressed and its degradation inhibited by lysosomal antiproteases. This study provides experimental evidence that links the effect of ferritin repression on growth stimulation to the expansion of the labile iron pool. (Blood. 2001;97:2863-2871)

PMID: 11313282, UI: 21213562

J Biol Chem 2001 Apr 11;

Intracellular chelation of iron by bipyridyl inhibits DNA virus replication: Ribonucleotide reductase maturation as a probe of intracellular iron pools.

Romeo AM, Christen L, Niles EG, Kosman DJ

Department of Biochemistry, SUNY at Buffalo, Buffalo, NY 14214.

[Record supplied by publisher]

Efficient replication of large DNA viruses requires dNTPs supplied by a viral ribonucleotide reductase. Viral ribonucleotide reductase is an early gene product of both vaccinia and herpes simplex virus. For productive infection, the apo-protein must scavenge iron from the endogenous, labile iron pool(s). The membrane-permeant, intracellular Fe2+ chelator, 2,2'-bipyridine (bipyridyl, BIP), is known to sequester iron from this pool. We show here that BIP strongly inhibits the replication of both vaccinia and herpes simplex virus (HSV-1). In a standard plaque assay, 50 mM BIP caused a 50% reduction in plaque forming units with either virus. Strong inhibition was observed only when BIP was added within 3 hours post infection (hpi). This time dependence was observed also in regards to inhibition of viral late protein and DNA synthesis by BIP. BIP did not inihibit the activity of vaccinia RR, its synthesis nor its stability indicating that BIP blocked the activation of the apo protein. In parallel with its inhibition of vaccinia RR activation, BIP treatment increased the RNA binding activity of the endogenous iron response protein, IRP1, by 1.9-fold. The data indicate that the diiron prosthetic group in vaccinia RR is assembled from iron taken from the BIP-accessible, labile iron pool that is sampled also by ferritin and the iron regulated protein found in the cytosol of mammalian cells.

PMID: 11301321