Disturbance of cellular iron uptake and utilisation by aluminium

Pérez, Gladys; Garbossa, Graciela; Risio, Cecilia Di; Vittori, Daniela; Nesse, Alcira

doi:10.1016/s0162-0134(01)00310-5

Cited by 18 publications

(20 citation statements)

References 22 publications

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“…The CA‐AM uptake and CA content depend on the membrane properties of the cells, their esterases content and activity as well as other factors that affect efflux and degradation. In the cells, various metal ions bind to CA and quench its fluorescence, depending on the ion concentrations and binding affinity (20–22); among these metals, iron is by far the most abundant (20). Thus, the basal CA fluorescence depends on the intracellular CA content and the amount of the labile (chelatable) iron pool (LIP).…”

Section: Discussionmentioning

confidence: 99%

Flow cytometry measurement of the labile iron pool in human hematopoietic cells

2007

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Iron is important for many biological processes, and its deficiency or excess is involved in pathological conditions. Although most iron is firmly bound (e.g., in hemoglobin), some, the labile iron pool (LIP), is bound to low-affinity ligands. The level of LIP is regulated to meet the cell's requirements for iron but prevent excess. We describe herein a multiparameter flow cytometry procedure for measuring LIP in various human hematopoietic cells. Peripheral blood and bone marrow (BM) cells were loaded with calcein-AM, washed, and then incubated with or without the high-affinity iron-chelator Deferiprone (L1). Specific cell subpopulations were identified based on side-light scattering and expression of surface antigens. LIP was determined based on the ability of L1 to bind and remove iron from calcein and thereby increase the fluorescence emitted by the cells. Blood cells differ in their LIP content in the order monocytes [ PMN [ RBC [ lymphocytes. Analysis of BM cells indicated a similar tendency among precursors of the different lineages. The results also showed that among myeloid precursors, LIP increases along cell maturation. Flow cytometry might be useful for evaluating LIP in various diseases and for studying the efficacy of iron-chelators.

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Section: Discussionmentioning

confidence: 99%

Flow cytometry measurement of the labile iron pool in human hematopoietic cells

2007

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“…39,40 Transferrinbound Fe(III), A1(III), Cr(III) or vanadium(V) can be internalised by cell-surface transferrin receptors. [41][42][43] Metal ions released from orthopaedic implants induce apoptosis and/ or necrosis in a range of cells, with Co(II) and V(III) among the most cytotoxic. 44,45 Corrosion products, including CoO, Cr 2 O 3 and CrPO 4 also show moderate cytotoxicity.…”

Section: Cellular Uptake and Biological Responses To Metal Wear Debrismentioning

confidence: 99%

Orthopaedic metals and their potential toxicity in the arthroplasty patient

Keegan

Learmonth

Case

2007

The Journal of Bone and Joint Surgery. British volume

293

196

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The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.

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“…Following absorption of Al via the gastrointestinal system, the metal gains entry to the liver, kidney, lungs, and spleen with the assistance of the transferrin uptake machinery or the involvement of organic chelators such as citrate, malate, lactate, or succinate [3]. In the transferrin-mediated uptake system, Al competes with Fe and gains access to the cell with the aid of the receptor-mediated endocytosis [5]. Once inside the cell, Al exerts its toxic properties by substituting for iron in Fe-dependent proteins, thus preventing redox reactions [6].…”

Section: Introductionmentioning

confidence: 99%

Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes

Mailloux

Hamel

Appanna

2006

J. Biochem. Mol. Toxicol.

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Aluminum (Al), a known environmental toxicant, has been linked to a variety of pathological conditions such as dialysis dementia, osteomalacia, Alzheimer's disease, and Parkinson's disease. However, its precise role in the pathogenesis of these disorders is not fully understood. Using hepatocytes as a model system, we have probed the impact of this trivalent metal on the aerobic energy-generating machinery. Here we show that Al-exposed hepatocytes were characterized by lipid and protein oxidation and a dysfunctional tricarboxylic acid (TCA) cycle. BN-PAGE, SDS-PAGE, and Western blot analyses revealed a marked decrease in activity and expression of succinate dehydrogenase (SDH), alpha-ketoglutarate dehydrogenase (KGDH), isocitrate dehydrogenase-NAD+ (IDH), fumarase (FUM), aconitase (ACN), and cytochrome c oxidase (Cyt C Ox). 13C-NMR and HPLC studies further confirmed the disparate metabolism operative in control and Al-stressed cells and provided evidence for the accumulation of succinate in the latter cultures. In conclusion, these results suggest that Al toxicity promotes a dysfunctional TCA cycle and impedes ATP production, events that may contribute to various Al-induced abnormalities.

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Disturbance of cellular iron uptake and utilisation by aluminium

Cited by 18 publications

References 22 publications

Flow cytometry measurement of the labile iron pool in human hematopoietic cells

Flow cytometry measurement of the labile iron pool in human hematopoietic cells

Orthopaedic metals and their potential toxicity in the arthroplasty patient

Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes

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