Thyroid hormone regulation of APP (b-amyloid precursor protein) gene expression in brain and brain cultured cells

We have previously shown that the thyroid hormone triiodothyronine negatively regulates the transcrip tional activity of the b-amyloid precursor protein gene (APP) in cultured murine neuroblastoma cells, by a mechanism that involves binding of the nuclear thyroid hormone receptor (TR) to DNA sequenc...

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Detalles Bibliográficos
Autores: Contreras Jurado, Silvia Constanza, Pascual, Angel
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad Alfonso X el Sabio
Repositorio:Repositorio Institucional de la Universidad Alfonso X el Sabio
Idioma:inglés
OAI Identifier:oai:archive.uax.com:20.500.12080/26179
Acceso en línea:https://hdl.handle.net/20.500.12080/26179
Access Level:acceso abierto
Palabra clave:Amyloid precursor protein ,Thyroid hormone, Hypothyroidism ,TR knockout, Brain
Descripción
Sumario:We have previously shown that the thyroid hormone triiodothyronine negatively regulates the transcrip tional activity of the b-amyloid precursor protein gene (APP) in cultured murine neuroblastoma cells, by a mechanism that involves binding of the nuclear thyroid hormone receptor (TR) to DNA sequences located within the first exon of the gene. In this report we present results showing that the thyroid hormones also repress the expression of APP in human neuroblastoma cells and in primary cultures of rat neurons. In addition, and in agreement with the results obtained in cultured cells, APP messenger RNA and protein levels are significantly higher in the brain of hypothyroid rats and mice, and also in Alzheimer-related brain regions dissected from KO mice lacking TRs. These results show that binding of the thyroid hor mones to their nuclear receptors mediate their repressive effect on APP gene expression in vivo

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