title: Short communication: the pharmacological peroxisome proliferator-activated receptor α agonist WY-14,643 increases expression of novel organic cation transporter 2 and carnitine uptake in bovine kidney cells.
abstract: Recent studies in rodents demonstrated that peroxisome proliferator-activated receptor α (PPARα), a central regulator of energy homeostasis, is an important transcriptional regulator of the gene encoding the carnitine transporter novel organic cation transporter 2 (OCTN2). Less is known with regard to the regulation of OCTN2 by PPARα and its role for carnitine transport in cattle, even though PPARα activation physiologically occurs in the liver of high-producing cows during early lactation. To explore the role of PPARα for OCTN2 expression and carnitine transport in cattle, we studied the effect of the PPARα activator WY-14,643 on the expression of OCTN2 in the presence and absence of PPARα antagonists and on OCTN2-mediated carnitine transport in the Madin-Darby bovine kidney (MDBK) cell line. The results show that WY-14,643 increases mRNA and protein levels of OCTN2, whereas co-treatment of MDBK cells with WY-14,643 and the PPARα antagonist GW6471 blocks the WY-14,643-induced increase in mRNA and protein levels of OCTN2 in bovine cells. In addition, treatment of MDBK cells with WY-14,643 stimulates specifically Na(+)-dependent carnitine uptake in MDBK cells, which is likely the consequence of the increased carnitine transport capacity of cells due to the elevated expression of OCTN2. In conclusion, our results indicate that OCTN2 expression and carnitine transport in cattle, as in rodents, are regulated by PPARα.
authors.affiliation: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, D-35392 Gießen, Germany.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, D-35392 Gießen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wen
authors.affiliation: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, D-35392 Gießen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Ringseis
authors.affiliation: Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-Universität Gießen, Heinrich-Buff-Ring 26-32, D-35392 Gießen, Germany. Electronic address: klaus.eder@ernaehrung.uni-giessen.de.
authors.forename: K
authors.initials: K
authors.lastname: Eder
mesh_terms: D000818:Animals; D002331:Carnitine / Q000493:pharmacokinetics*; D002417:Cattle; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D007668:Kidney / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D047493:PPAR alpha / Q000819:agonists*; D011743:Pyrimidines / Q000819:agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014803:Vitamin B Complex / Q000493:pharmacokinetics
chemical_list: D027701:Organic Cation Transport Proteins; D047493:PPAR alpha; D011743:Pyrimidines; D012333:RNA, Messenger; D014803:Vitamin B Complex; C006253:pirinixic acid; D002331:Carnitine
keywords: bovine kidney cells; novel organic cation transporter 2; peroxisome proliferator-activated receptor α