Decreased cell proliferation and higher oxidative stress in fibroblasts from Down Syndrome fetuses. Preliminary study.
Biochim Biophys Acta
; 1842(1): 116-25, 2014 Jan.
Article
en En
| MEDLINE
| ID: mdl-24184606
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.
Palabras clave
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
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piel
/
Síndrome de Down
/
Estrés Oxidativo
/
Fibroblastos
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2014
Tipo del documento:
Article