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An altered antioxidant balance occurs in Down syndrome fetal organs: Implications for the “gene dosage effect” hypothesis

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Advances in Down Syndrome Research

Part of the book series: Journal of Neural Transmission Supplement 67 ((NEURAL SUPPL,volume 67))

Summary

Down syndrome (DS) is the congenital birth defect responsible for the greatest number of individuals with mental retardation. It arises due to trisomy of human chromosome 21 (HSA21) or part thereof. To date there have been limited studies of HSA21 gene expression in trisomy 21 conceptuses. In this study we investigate the expression of the HSA21 antioxidant gene, Cu/Zn-superoxide dismutase-1 (SOD1) in various organs of control and DS aborted conceptuses. We show that SOD1 mRNA levels are elevated in DS brain, lung, heart and thymus. DS livers show decreased SOD1 mRNA expression compared with controls. Since non-HSA21 antioxidant genes are reported to be concomitantly upregulated in certain DS tissues, we examined the expression of glutathione peroxidase-1 (GPX1) in control and DS fetal organs. Interestingly, GPX1 expression was unchanged in the majority of DS organs and decreased in DS livers. We examined the SOD1 to GPX1 mRNA ratio in individual organs, as both enzymes form part of the body’s defense against oxidative stress, and because a disproportionate increase of SOD1 to GPX1 results in noxious hydroxyl radical damage. All organs investigated show an approximately 2-fold increase in the SOD1 to GPX1 mRNA ratio. We propose that it is the altered antioxidant ratio that contributes to certain aspects of the DS phenotype.

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Abbreviations

SOD1:

human Cu/Zn-superoxide dismutase

GPX1:

human selenium-dependent glutathione peroxidase

DS:

Down syndrome

HSA21:

human chromosome 21

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Authors and Affiliations

  1. Monash Institute of Reproduction and Development, Centre for Functional Genomics and Human Disease, Monash University, Clayton Victoria, Australia

    J. B. de Haan & M. Pritchard

  2. Baker Heart Research Institute, Diabetic Complications Group, Commercial Rd., Prahran, 3181, Australia

    J. B. de Haan

  3. Department of Pathology, Monash Medical Centre, Clayton Victoria, Australia

    B. Susil

  4. Merck Research Laboratories, Merck & Co., Inc, Rahway, NJ, USA

    I. Kola

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  1. J. B. de Haan
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  2. B. Susil
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  3. M. Pritchard
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  4. I. Kola
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Editors and Affiliations

  1. Department of Pediatrics, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    G. Lubec

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de Haan, J.B., Susil, B., Pritchard, M., Kola, I. (2003). An altered antioxidant balance occurs in Down syndrome fetal organs: Implications for the “gene dosage effect” hypothesis. In: Lubec, G. (eds) Advances in Down Syndrome Research. Journal of Neural Transmission Supplement 67, vol 67. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6721-2_6

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  • DOI: https://doi.org/10.1007/978-3-7091-6721-2_6

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  • Print ISBN: 978-3-211-40776-9

  • Online ISBN: 978-3-7091-6721-2

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