Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor

Autor: Martin Göttlicher, E Widmark, Qiao Li, Jan-Åke Gustafsson
Rok vydání: 1992
Předmět:
Peroxisome proliferator-activated receptor gamma
Placenta
Recombinant Fusion Proteins
Molecular Sequence Data
Receptors
Cytoplasmic and Nuclear
Peroxisome proliferator-activated receptor
Receptors
Cell Surface
CHO Cells
Fatty Acids
Nonesterified
Biology
Transfection
Polymerase Chain Reaction
Dexamethasone
Receptors
Glucocorticoid
Pregnancy
Cricetinae
Animals
Humans
5-HT5A receptor
Amino Acid Sequence
Clofibrate
Unsaturated fatty acid
chemistry.chemical_classification
Multidisciplinary
Base Sequence
Chimera
Anticholesteremic Agents
DNA
Dehydroepiandrosterone
Alkaline Phosphatase
Molecular biology
Rats
Kinetics
Cholesterol
Pyrimidines
Oligodeoxyribonucleotides
chemistry
Nuclear receptor
Biochemistry
Fatty Acids
Unsaturated
Nuclear receptor coactivator 2
Free fatty acid receptor
Female
Peroxisome proliferator-activated receptor alpha
Transcription Factors
Research Article
Zdroj: Proceedings of the National Academy of Sciences. 89:4653-4657
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.89.10.4653
Popis: Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate PPAR (peroxisome proliferator-activated receptor), a member of the steroid nuclear receptor superfamily. We have cloned the cDNA from the rat that is homologous to that from the mouse [Issemann, I. & Green, S. (1990) Nature (London) 347, 645-650], which encodes a 97% similar protein with a particularly well-conserved putative ligand-binding domain. To search for physiologically occurring activators, we established a transcriptional transactivation assay by stably expressing in CHO cells a chimera of rat PPAR and the human glucocorticoid receptor that activates expression of the placental alkaline phosphatase reporter gene under the control of the mouse mammary tumor virus promoter. Testing of compounds related to lipid metabolism or peroxisomal proliferation revealed that 150 microM concentrations of arachidonic or linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy-cholesterol, activate the receptor chimera. In addition, saturated fatty acids induce the reporter gene. Shortening the chain length to n = 6 or introduction of an omega-terminal carboxylic group abolished the activation potential of the fatty acid. In conclusion, the present results indicate that fatty acids can regulate gene expression mediated by a member of the steroid nuclear receptor superfamily.
Databáze: OpenAIRE
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