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Iron inhibits neurotoxicity

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General fitness, health and nutrition
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7 February 2004
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  1. Jesus consumed iron.

    Quoted message said:

    J Biol Inorg Chem. 2004 Feb 3

    Iron inhibits neurotoxicity induced by trace copper and biological reductants.

    White AR, Barnham KJ, Huang X, Voltakis I, Beyreuther K, Masters CL, Cherny RA, Bush AI, Cappai R.

    Department of Pathology and Centre for Neuroscience, The University of Melbourne, 3010, Carlton
    South, Victoria, Australia.

    The extracellular microenvironment of the brain contains numerous biological redox agents,
    including ascorbate, glutathione, cysteine and homocysteine. During ischemia/reperfusion, aging or
    neurological disease, extracellular levels of reductants can increase dramatically owing to
    dysregulated homeostasis. The extracellular concentrations of transition metals such as copper and
    iron are also substantially elevated during aging and in some neurodegenerative disorders.
    Increases in the extracellular redox capacity can potentially generate neurotoxic free radicals
    from reduction of Cu(II) or Fe(III), resulting in neuronal cell death. To investigate this in
    vitro, the effects of extracellular reductants (ascorbate, glutathione, cysteine, homocysteine or
    methionine) on primary cortical neurons was examined. All redox agents except methionine induced
    widespread neuronal oxidative stress and subsequent cell death at concentrations occurring in
    normal conditions or during neurological insults. This neurotoxicity was totally dependent on trace
    Cu (>/=0.4 microM) already present in the culture medium and did not require addition of exogenous
    Cu. Toxicity involved generation of Cu(I) and H(2)O(2), while other trace metals did not induce
    toxicity. Surprisingly, administration of Fe(II) or Fe(III) (>/=2.5 microM) completely abrogated
    reductant-mediated neurotoxicity. The potent protective activity of Fe correlated with Fe
    inhibiting reductant-mediated Cu(I) and H(2)O(2) generation in cell-free assays and reduced
    cellular Cu uptake by neurons. This demonstrates a novel role for Fe in blocking Cu-mediated
    neurotoxicity in a high reducing environment. A possible pathogenic consequence for these phenomena
    was demonstrated by abrogation of Fe neuroprotection after pre-exposure of cultures to the
    Alzheimer's amyloid beta peptide (Abeta). The loss of Fe neuroprotection against reductant toxicity
    was greater after treatment with human Abeta1-42 than with human Abeta1-40 or rodent Abeta1-42,
    consistent with the central role of Abeta1-42 in Alzheimer's disease. These findings have important
    implications for trace biometal interactions and free radical-mediated damage during
    neurodegenerative illnesses such as Alzheimer's disease and old-age dementia.

    PMID: 14758525 [PubMed - as supplied by publisher]

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