Iron inhibits neurotoxicity

Discussion in 'Food and nutrition' started by irondoe, Feb 6, 2004.

  1. irondoe

    irondoe Guest

    Jesus consumed iron.

    >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]