Abstract
Retinoic acid (RA) is a potent regulator of morphogenesis, growth and cell differentiation. Incubation with RA causes arrest of proliferation and neurite extension in SH-SY5Y cells, a neuroblastoma cell line of human origin. In these cells, RA regulates the expression of the beta-amyloid precursor protein. The retinoid increases the levels of intracellular and secreted forms of APP (amyloid precursor protein), APP-mRNA levels and the activity of the APP promoter in transient transfection studies. These responses require long periods of exposition to the ligand, thus suggesting a nondirect effect of the RA receptors on the APP gene. Also in these cells, RA induces the expression of TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor (BDNF), and 4 days of pretreatment with retinoic acid confers BDNF responsiveness to the APP promoter.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Protein Precursor / metabolism*
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Autoradiography
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Blotting, Northern
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Blotting, Western
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Brain-Derived Neurotrophic Factor / metabolism*
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Cell Differentiation / drug effects
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Cell Division / drug effects
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Chloramphenicol O-Acetyltransferase / metabolism
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Drug Interactions
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Gene Expression Regulation / drug effects*
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Humans
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Neuroblastoma / genetics*
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RNA, Messenger / metabolism
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Receptor Protein-Tyrosine Kinases / biosynthesis*
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Receptor, trkB / genetics
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Receptor, trkB / metabolism
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Thymidine / metabolism
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Time Factors
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Transfection / methods
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Tretinoin / pharmacology*
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Tritium / metabolism
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Tumor Cells, Cultured
Substances
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Amyloid beta-Protein Precursor
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Brain-Derived Neurotrophic Factor
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RNA, Messenger
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Tritium
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Tretinoin
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Chloramphenicol O-Acetyltransferase
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Receptor Protein-Tyrosine Kinases
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Receptor, trkB
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Thymidine