Modulation of the Expression of Peroxisome Proliferator-Activated Receptor-Dependent Genes through Disproportional Expression of Two Subtypes in the Small Intestine

Autor: Masaaki Kitagawa, Sachiko Takase, Kazuhito Suruga, Toshinao Goda, Kazuki Mochizuki
Rok vydání: 2001
Předmět:
Male
Receptors
Retinoic Acid
Biophysics
Receptors
Cytoplasmic and Nuclear
Peroxisome proliferator-activated receptor
Nerve Tissue Proteins
Regulatory Sequences
Nucleic Acid
Biology
Retinoid X receptor
Fatty Acid-Binding Proteins
Binding
Competitive
Biochemistry
Intestine
Small
medicine
Animals
Protein Isoforms
RNA
Messenger
Rats
Wistar
Receptor
Molecular Biology
Gene
Triglycerides
chemistry.chemical_classification
Oxidase test
Dose-Response Relationship
Drug
Retinol-Binding Proteins
Cellular
Peroxisome
Dietary Fats
Molecular biology
Small intestine
Neoplasm Proteins
Rats
Retinol-Binding Proteins
Retinoic acid receptor
Jejunum
Retinoid X Receptors
medicine.anatomical_structure
Gene Expression Regulation
chemistry
Electrophoresis
Polyacrylamide Gel
lipids (amino acids
peptides
and proteins)
Carrier Proteins
Fatty Acid-Binding Protein 7
Dimerization
Transcription Factors
Zdroj: Archives of Biochemistry and Biophysics. 389:41-48
ISSN: 0003-9861
DOI: 10.1006/abbi.2001.2305
Popis: We have reported that dietary long-chain triacylglycerols (LCT) enhance the transcription of cellular retinol-binding protein, the type II (CRBPII) gene, and the liver-type fatty acid-binding protein (L-FABP) gene in the small intestine. Because the cis elements on the CRBPII gene consisting of two AGGTCA motifs separated by a single nucleotide are known to bind not only the 9-cis-retinoic acid receptor (RXR) homodimer, but also the peroxisome proliferator-activated receptor (PPAR)-RXR heterodimer, it has been implicated that the unsaturated long-chain fatty acids, as the ligands of the PPAR, might activate the transcription of the CRBPII gene, thereby making use of the RXR-response elements (RXRE and RE3) as the PPAR-response element (PPRE). In this study, we found that the PPARalpha mRNA level in the rat jejunum was elevated by dietary fat, whereas the PPARdelta mRNA level was reduced under this condition. Electrophoretic mobility-shift assay revealed that both PPARalpha-RXRalpha and PPARdelta-RXRalpha heterodimers, specifically and in a dose-dependent manner, bound to the two PPRE-like elements of the rat CRBPII gene as well as the known PPREs in the L-FABP and acyl-CoA oxidase genes. The binding of the PPARalpha-RXRalpha heterodimer to the CRBPII-RXRE, the CRBPII-RE3, and the PPREs of L-FABP, HMG-CoA synthase, and acyl-CoA oxidase was gradually diminished by the addition of increasing amounts of PPARdelta. The binding of the PPARdelta-RXRalpha heterodimer to CRBPII-RXRE, CRBPII-RE3, and other PPREs was also gradually reduced by the addition of increasing amounts of PPARalpha. Using Escherichia coli-expressed RXRalpha, we showed that the mutual competition for RXRalpha with PPARalpha and PPARdelta occurred at the protein level. These results suggest that the transcriptions of CRBPII, L-FABP, and the other PPAR-dependent genes in the small intestine may be coordinately regulated by the disproportional expression of PPARalpha and PPARdelta.
Databáze: OpenAIRE
Externí odkaz: