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Metals and Paraoxonases

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Neurotoxicity of Metals

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 18))

Abstract

The paraoxonases (PONs) are a three-gene family which includes PON1, PON2, and PON3. PON1 and PON3 are synthesized primarily in the liver and a portion is secreted in the plasma, where they are associated with high-density lipoproteins (HDLs), while PON2 is an intracellular enzyme, expressed in most tissues and organs, including the brain. PON1 received its name from its ability to hydrolyze paraoxon, the active metabolite of the organophosphorus (OP) insecticide parathion, and also more efficiently hydrolyzes the active metabolites of several other OPs. PON2 and PON3 do not have OP-esterase activity, but all PONs are lactonases and are capable of hydrolyzing a variety of lactones, including certain drugs, endogenous compounds, and quorum-sensing signals of pathogenic bacteria. In addition, all PONs exert potent antioxidant effects. PONs play important roles in cardiovascular diseases and other oxidative stress-related diseases, modulate susceptibility to infection, and may provide neuroprotection (PON2). Hence, significant attention has been devoted to their modulation by a variety of dietary, pharmacological, lifestyle, or environmental factors. A number of metals have been shown in in vitro, animal, and human studies to mostly negatively modulate expression of PONs, particularly PON1, the most studied in this regard. In addition, different levels of expression of PONs may affect susceptibility to toxicity and neurotoxicity of metals due to their aforementioned antioxidant properties.

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Abbreviations

Ag:

Silver

Al:

Aluminum

As:

Arsenic

Ba:

Barium

Cd:

Cadmium

Ce:

Cesium

Co:

Cobalt

Cr:

Chromium

Cu:

Copper

Fe:

Iron

Gd:

Gadolinium

HDL:

High-density lipoprotein

Hg:

Mercury

L:

Leucine

La:

Lanthanum

LDL:

Low-density lipoprotein

M:

Methionine

MeHg:

Methylmercury

Mn:

Manganese

Ni:

Nickel

OP:

Organophosphate

Pb:

Lead

PCR:

Polymerase chain reaction

PON:

Paraoxonase

ppb:

Parts per billion

ppm:

Parts per million

Q:

Glutamine

R:

Arginine

Sm:

Samarium

Y:

Yttrium

Zn:

Zinc

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Acknowledgments

Studies by the authors were supported in part by grants from NIEHS (P42ES004696, P30ES007033). We thank Dr. Wan-Fen Li and Ms. Rebecca Richter for their help with some of the experiments shown in Figs. 1, 2, and 3 and Dr. Renee LeBoeuf for providing the tissues of experiments shown in Fig. 4.

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Authors and Affiliations

  1. Department of Environmental and Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA, 98105, USA

    Lucio G. Costa, Toby B. Cole & Jacqueline M. Garrick

  2. Department of Medicine & Surgery, University of Parma, Parma, Italy

    Lucio G. Costa

  3. Center on Human Development and Disability, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA, 98105, USA

    Toby B. Cole

  4. Department of Medicine (Division of Medical Genetics), University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA, 98105, USA

    Judit Marsillach & Clement E. Furlong

  5. Department of Genome Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA, 98105, USA

    Clement E. Furlong

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  1. Lucio G. Costa
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Correspondence to Lucio G. Costa .

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  1. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA

    Michael Aschner

  2. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA

    Lucio G. Costa

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Costa, L.G., Cole, T.B., Garrick, J.M., Marsillach, J., Furlong, C.E. (2017). Metals and Paraoxonases. In: Aschner, M., Costa, L. (eds) Neurotoxicity of Metals. Advances in Neurobiology, vol 18. Springer, Cham. https://doi.org/10.1007/978-3-319-60189-2_5

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