PPARalpha agonists positively and negatively regulate the expression of several nutrient/drug transporters in mouse small intestine.
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.
Hirai
Toshitake
T
Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
Fukui
Yuka
Y
Motojima
Kiyoto
K
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D003066:Coenzyme A Ligases / Q000235:genetics*; D005786:Gene Expression Regulation; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D047493:PPAR alpha / Q000819:agonists*; D060347:Sodium-Coupled Vitamin C Transporters; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters / Q000235:genetics*
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D003066:Coenzyme A Ligases; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027701:Organic Cation Transport Proteins; D047493:PPAR alpha; D060347:Sodium-Coupled Vitamin C Transporters; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; C489271:Abcd3 protein, mouse; C501412:Abcg2 protein, mouse; C492019:Slc22a5 protein, mouse; C525186:FATP2 protein, mouse; C525187:Mct13 protein, mouse; C421109:multidrug resistance-associated protein 1