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Elucidation of the Zinc-Finger Motif as a Target for Heavy-Metal Perturbations

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Handbook of Neurotoxicology

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Abstract

Essential and nonessential metals are redistributed naturally in the environment by both geological and biological cycles, however, industrial activities have greatly increased the health risks associated with exposure to heavy metals. Once absorbed into the body, metals can target multiple organs and interfere with a number of cellular processes. To regulate such actions, the body has developed elaborate macromolecules to store, channel, transport, chelate, and complex such metals and has tailored protein-metal interactions to fit the exact physiochemical properties and dimensions of essential metal cations. Therefore when biomolecules encounter toxic metals with no biological function and that depart from these exact specifications, the interaction is likely to produce an undesirable outcome. Thus, traditional research has been focused on the effects of heavy metals on neurotransmitters and ion-channel function, enzyme catalysis, and metal-mediated generation of free radicals (1–3). Little information exists on the effects of heavy metals on proteins that contain structural repeats that are stabilized and coordinated by metal cations such as Zn. While the majority of such proteins are involved in some type of protein-nucleic acid interactions such as regulation of gene expression and DNA repair (4,5), a number of cellular enzymes and metal-binding proteins contain cysteine-rich motifs that interact with Zn ions as part of their function (6). Studies have shown that factors containing such motifs could be potential targets for perturbation by heavy metals (5,7–10). Furthermore, work from our laboratory has found that exposure to metals such as Pb, Cd, and Hg interfere with the DNA-binding properties of Sp1 and the expression of its target genes (11,12).

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Authors
  1. Nasser H. Zawia
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  2. Morad Razmiafshari
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Editors and Affiliations

  1. The National Health and Environmental Effects Research Laboratory, Research Triangle Park, Durham, NC, USA

    Edward J. Massaro

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Zawia, N.H., Razmiafshari, M. (2002). Elucidation of the Zinc-Finger Motif as a Target for Heavy-Metal Perturbations. In: Massaro, E.J. (eds) Handbook of Neurotoxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-132-9_9

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  • DOI: https://doi.org/10.1007/978-1-59259-132-9_9

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-193-6

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