title: Decreased cell proliferation and higher oxidative stress in fibroblasts from Down Syndrome fetuses. Preliminary study.
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.
authors.affiliation: Department of Anatomy and Human Embryology, Faculty of Medicine, University of Valencia, Av/Blasco Ibáñez, 15, E46010 Valencia, Spain; Fundación Investigación Hospital Clínico Universitario de Valencia, Instituto de Investigación INCLIVA, Avda. Blasco Ibáñez 17, E46010 Valencia, Spain. Electronic address: gimenoa@uv.es.
authors.forename: Amparo
authors.initials: A
authors.lastname: Gimeno
authors.forename: José Luis
authors.initials: JL
authors.lastname: García-Giménez
authors.forename: Laura
authors.initials: L
authors.lastname: Audí
authors.forename: Nuria
authors.initials: N
authors.lastname: Toran
authors.forename: Pilar
authors.initials: P
authors.lastname: Andaluz
authors.forename: Francisco
authors.initials: F
authors.lastname: Dasí
authors.forename: José
authors.initials: J
authors.lastname: Viña
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
mesh_terms: D002374:Catalase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D061251:Primary Cell Culture; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059505:Telomere Homeostasis; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D054477:Glutaredoxins; C000606290:SOD1 protein, human; D013879:Thioredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione
keywords: BrdU; Cu/Zn superoxide dismutase; Cu/ZnSOD; DHR; DS; Down Syndrome; GAPDH; GPx; Glutathione; Grx1; Mn superoxide dismutase; MnSOD; Progeroid; ROS; Rcan1; Superoxide dismutase; TL; Telomere length; Thioredoxin; Trx1; bromodeoxyuridine; dihydrorhodamine; glutaredoxin 1; glutathione peroxidase; glyceraldehyde-3-phosphate dehydrogenase; reactive oxygen species; telomere length; thioredoxin 1