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Modulation of the expression of peroxisome proliferator-activated receptor-dependent genes through disproportional expression of two subtypes in the small intestine.

Abstract：

: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.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Mochizuki K,Suruga K,Kitagawa M,Takase S,Goda T

doi

10.1006/abbi.2001.2305

subject

Has Abstract

pub_date

2001-05-01 00:00:00

pages

41-8

issue

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(01)92305-7

journal_volume

389

pub_type

杂志文章

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Modulation of the expression of peroxisome proliferator-activated receptor-dependent genes through disproportional expression of two subtypes in the small intestine.