RESUMEN
Nutritional selenium deficiency is associated with Keshan disease in humans and white muscle disease in ruminant livestock. In this study, mice were fed a selenium-deficient diet for three generations. Female mice from the third depleted generation of these mice were given water containing either no added selenium or 0.1 or 1.0 ppm selenium as sodium selenate; DNA microarrays were used to compare gene expression in the muscle from mice fed the selenium diets to that from mice remaining on the depleted diet. The most prominent expression increases were observed with Ptger2 (a prostaglandin E receptor), Tcrb-V13 (a T-cell receptor beta), Tcf-7 (a T-cell transcription factor), and Lck (lymphocyte protein tyrosine kinase), and the major consistent decrease was Vav2, an oncogene in mice consuming the selenium containing diets.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Análisis de Secuencia por Matrices de Oligonucleótidos , Selenio/administración & dosificación , Selenio/deficiencia , Animales , ADN/análisis , ADN/metabolismo , Suplementos Dietéticos , Femenino , Factor Nuclear 1-alfa del Hepatocito , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/biosíntesis , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/genética , Ratones , Ratones Endogámicos , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogénicas c-vav/biosíntesis , Proteínas Proto-Oncogénicas c-vav/genética , Receptores de Antígenos de Linfocitos T alfa-beta/biosíntesis , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Prostaglandina E/biosíntesis , Receptores de Prostaglandina E/genética , Selenio/farmacología , Factor 1 de Transcripción de Linfocitos T/biosíntesis , Factor 1 de Transcripción de Linfocitos T/genética , Factores de Transcripción/biosíntesis , Factores de Transcripción/genéticaRESUMEN
To identify regulatory elements in the rat selenoprotein W (SeW) promoter, 2090, 1265, 741, and 404 base pair truncations of genomic DNA lying immediately upstream of the SeW coding sequence were cloned into a luciferase reporter vector (pGL3-Basic from Promega, Madison, WI, USA). 3656 and 406 base pair mouse SeW promoter constructs were also compared. SeW promoter activity was assayed in two rat cell lines: L8 muscle cells and C6 brain cells. The SeW promoter was 2-7 times more active (p<0.01) than SV40 promoter. Promoter activity of constructs of the SeW promoter ranging from 200 base pairs to 51 base pairs gradually decreased to zero in brain cells, but fell precipitously to zero in muscle cells. Some truncations stimulated promoter activity, suggesting the full-length promoter may contain binding sites for factors that suppress SeW expression.
