title: Thyroid hormone regulation of APP (β-amyloid precursor protein) gene expression in brain and brain cultured cells.
abstract: We have previously shown that the thyroid hormone triiodothyronine negatively regulates the transcriptional activity of the β-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 hormones to their nuclear receptors mediate their repressive effect on APP gene expression in vivo.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain.
authors.forename: Constanza
authors.initials: C
authors.lastname: Contreras-Jurado
authors.forename: Angel
authors.initials: A
authors.lastname: Pascual
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism; D013963:Thyroid Hormones / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D017931:DNA Primers; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones