PPARalpha agonists positively and negatively regulate the expression of several nutrient/drug transporters in mouse small intestine

Biol Pharm Bull. 2007 Nov;30(11):2185-90. doi: 10.1248/bpb.30.2185.

Abstract

A systematic analysis to examine the effects of peroxisome proliferator-activated receptor (PPAR)alpha agonists on the expression levels of all the nutrient/drug plasma-membrane transporters in the mouse small intestine was performed. Transporter mRNAs that were induced or repressed by two independent PPARalpha-specific agonists were identified by a genome-wide microarray method, and the changes were confirmed by real-time PCR using RNA isolated from the intestines and livers of wild-type and PPARalpha-null mice. Expression levels of seven nutrient/drug transporters (Abcd3, Octn2/Slc22a5, FATP2/Slc27a2, Slc22a21, Mct13/Slc16a13, Slc23a1 and Bcrp/Abcg2) in the intestine were up-regulated and the expression level of one (Mrp1/Abcc1) was down-regulated by PPARalpha; although the previously report that the H(+)/peptide co-transporter 1 (Pept1) is up-regulated by PPARalpha was not replicated in our study. We propose that the transport processes can be coordinately regulated with intracellular metabolism by nutrient nuclear receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Coenzyme A Ligases / genetics*
  • Gene Expression Regulation*
  • Intestine, Small / metabolism*
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Monocarboxylic Acid Transporters / genetics*
  • Multidrug Resistance-Associated Proteins / genetics*
  • Organic Anion Transporters, Sodium-Dependent / genetics*
  • Organic Cation Transport Proteins / genetics*
  • PPAR alpha / agonists*
  • Sodium-Coupled Vitamin C Transporters
  • Solute Carrier Family 22 Member 5
  • Symporters / genetics*

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcd3 protein, mouse
  • Abcg2 protein, mouse
  • Membrane Proteins
  • Monocarboxylic Acid Transporters
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Organic Cation Transport Proteins
  • PPAR alpha
  • Slc22a5 protein, mouse
  • Sodium-Coupled Vitamin C Transporters
  • Solute Carrier Family 22 Member 5
  • Symporters
  • Coenzyme A Ligases
  • FATP2 protein, mouse
  • Mct13 protein, mouse
  • multidrug resistance-associated protein 1