Decreased cell proliferation and higher oxidative stress in fibroblasts from down syndrome fetuses. Preliminary study

Amparo Gimeno, José Luis García-Giménez, Laura Audí, Nuria Toran, Pilar Andaluz, Francisco Dasí, José Viña, Federico V. Pallardó

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    29 Citations (Scopus)

    Abstract

    Down Syndrome is the most common chromosomal disease and is also known for its decreased incidence of solid tumors and its progeroid phenotype. Cellular and systemic oxidative stress has been considered as one of the Down Syndrome phenotype causes. We correlated, in a preliminary study, the fibroblast proliferation rate and different cell proliferation key regulators, like Rcan1 and the telomere length from Down Syndrome fetuses, with their oxidative stress profile and the Ribonucleic acid and protein expression of the main antioxidant enzymes together with their activity. Increased oxidized glutathione/glutathione ratio and high peroxide production were found in our cell model. These results correlated with a distorted antioxidant shield. The messenger RNA (. SOD1) and protein levels of copper/zinc superoxide dismutase were increased together with a decreased mRNA expression and protein levels of glutathione peroxidase (GPx). As a consequence the [Cu/ZnSOD. /. (catalase. +. GPx)] activity ratio increases which explains the oxidative stress generated in the cell model. In addition, the expression of thioredoxin 1 and glutaredoxin 1 is decreased. The results obtained show a decreased antioxidant phenotype that correlates with increased levels of Regulator of calcineurin 1 and attrition of telomeres, both related to oxidative stress and cell cycle impairment. Our preliminary results may explain the proneness to a progeroid phenotype. © 2013 Elsevier B.V.
    Original languageEnglish
    Pages (from-to)116-125
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1842
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2014

    Keywords

    • Glutathione
    • Progeroid
    • Rcan1
    • Superoxide dismutase
    • Telomere length
    • Thioredoxin

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