OCTN2-mediated carnitine uptake in a newly discovered human proximal tubule cell line (Caki-1)

Molecular Pharmaceutics

Volumn 4, Issue 1, 2007, Pages 160-168

  Glube, Natalie ^a   Closs, Ellen ^a   Langguth, Peter ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

Caki 1; L carnitine; OCTN2; Proximal tubule; Renal secretion

Indexed keywords

AMMONIUM DERIVATIVE; CARNITINE; CARRIER PROTEIN; CEFALORIDINE; CETIRIZINE; CICLOTROPIUM BROMIDE; CIMETIDINE; FAMOTIDINE; IPRATROPIUM BROMIDE; METFORMIN; OCTAMER TRANSCRIPTION FACTOR; PROTEIN OCTN2; UNCLASSIFIED DRUG; VALPROIC ACID;

ARTICLE; CONTROLLED STUDY; DRUG ANTAGONISM; DRUG STRUCTURE; DRUG UPTAKE; HUMAN; HUMAN CELL; ISOTOPE LABELING; KIDNEY PROXIMAL TUBULE; PRIORITY JOURNAL;

BIOLOGICAL TRANSPORT; CADHERINS; CARNITINE; FLUORESCENT ANTIBODY TECHNIQUE; GENE EXPRESSION REGULATION; HUMANS; HYDROGEN-ION CONCENTRATION; KIDNEY TUBULES, PROXIMAL; ORGANIC CATION TRANSPORT PROTEINS; PHARMACEUTICAL PREPARATIONS; SODIUM; TEMPERATURE;

EID: 33847213858     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp060073a     Document Type: Article

References (26)

1. Elimrani, I.; Lahjouji, K.; Seidman, E.; Roy, M. J.; Mitchell, G. A.; Qureshi, I. Expression and localization of organic cation/carnitine transporter OCTN2 in Caco-2 cells. Am. J. Physiol.: Gastrointest. Liver Physiol. 2003, 284, G863-G871.
2. Bremer, J. Carnitine - metabolism and functions. Physiol. Rev. 1983, 63, 1420-1480.
3. Rebouche, C. J. Carnitine function and requirements during the life cycle. FASEB J. 1992, 6, 3379-3386.
4. Inano, A.; Sai, Y.; Nikaido, H.; Hasimoto, N.; Asano, M.; Tsuji, A.; Tamai, I. Acetyl-L-carnitine permeability across the blood-brain barrier and involvement of carnitine transporter OCTN2. Biopharm. Drug Dispos. 2003, 24, 357-365.
5. Tamai, I. Yabuuchi, H.; Nezu, J.; Sai, Y.; Oku, A.; Shimane, M.; Tsuji, A. Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett 1997, 419, 107-111.
6. Tamai, I.; Ohashi, R.; Nezu, J. I.; Sai, Y.; Kobayashi, D.; Oku, A.; Shimane, M.; Tsuji, A. Molecular and functional characterization of organic cation/carnitine transporter family in mice. J. Biol. Chem. 2000, 275, 40064-40072.
7. Sekine, T.; Cha, S. H.; Endou, H. The multispecific organic anion transporter (OAT) family. Pfluegers Arch. 2000, 440, 337-350.
8. Tamai, I.; Ohashi, R.; Nezu, J.; Yabuuchi, H.; Oku, A.; Shimane, M.; Sai, Y.; Tsuji, A. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J. Biol. Chem. 1998, 273, 20378-20382.
9. Sekine, T.; Kusuhara, H.; Utsunomiya-Tate, N.; Tsuda, M.; Sugiyama, Y.; Kanai, Y.; Endou, H. Molecular cloning and characterization of high-affinity carnitine transporter from rat intestine. Biochem. Biophys. Res. Commun. 1998, 251, 586-591.
10. Koizumi, A.; Nozaki, J.; Ohura, T.; Kayo, T.; Wada, Y.; Nezu, J.; Ohashi, R.; Tamai, I.; Shoji, Y.; Takada, G.; Kibira, S.; Matsuishi, T.; Tsuji, A. Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum. Mol. Genet. 1999, 8, 2247-2254.
11. Nezu, J.; Tamai, I.; Oku, A.; Ohashi, R.; Yabuuchi, H.; Hashimoto, N.; Nikaido, H.; Sai, Y.; Koizumi, A.; Shoji, Y.; Takada, G.; Matsuishi, T.; Yoshino, M.; Kato, H.; Ohura, T.; Tsujimoto, G.; Hayakawa, J.; Shimane, M.; Tsuji, A. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat. Genet. 1999, 21, 91-94.
12. Ohashi, R.; Tamai, I.; Nezu, Ji, J.; Nikaido, H.; Hashimoto, N.; Oku, A.; Sai, Y.; Shimane, M.; Tsuji, A. Molecular and physiological evidence for multifunctionality of carnitine/organic cation transporter OCTN2. Mol. Pharmacol. 2001, 59, 358-366.
13. Gomez-Amores, L.; Mate, A.; Vazquez, C. M. L-carnitine transport in kidney of normotensive, Wistar-Kyoto rats: effect of chronic L-carnitine administration. Pharm. Res. 2003, 20, 1133-1140.
14. Lahjouji, K.; Elimrani, I.; Lafond, J.; Leduc, L.; Qureshi, I. A.; Mitchell G. A. L-Carnitine transport in human placental brush-border membranes is mediated by the sodium-dependent organic cation transporter OCTN2. Am. J. Physiol.: Cell Physiol. 2004, 287, C263-C269.
15. Wu, X.; Huang, W.; Prasad, P. D., Seth, P.; Rajan, D. P.; Leibach, F. H.; Chen, J.; Conway, S. J.; Ganapathy, V. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J. Pharmacol. Exp. Ther. 1999, 290, 1482-1492.
16. Ganapathy, M. E.; Huang, W.; Rajan, D. P.; Carter, A. L.; Sugawara, M.; Iseki, K.; Leibach, F. H.; Ganapathy, V. beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J. Biol. Chem. 2000, 275, 1699-1707.
17. Friedrich, A.; Prasad, P. D.; Freyer, D.; Ganapathy, V.; Brust, P. Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells, an in vitro model of the bloodbrain barrier. Brain Res. 2003, 968, 69-79.
18. Stieger, B.; O'Neill, B.; Krahenbuhl, S. Characterization of L-carnitine transport by rat kidney brush-border-membrane vesicles. Biochem. J. 1995, 309 (Part 2), 643-647.
19. Huang, W.; Shaikh, S. N.; Ganapathy, M. E.; Hopfer, U.; Leibach, F. H.; Carter, A. L.; Ganapathy, V. Carnitine transport and its inhibition by sulfonylureas in human kidney proximal tubular epithelial cells. Biochem. Pharmacol. 1999, 58, 1361-1370.
20. Rytting, E.; Audus, K. L. Novel organic cation transporter 2-mediated carnitine uptake in placental choriocarcinoma (BeWo) cells. J. Pharmacol. Exp. Ther. 2005, 312, 192-198.
21. Wu, X.; Prasad, P. D.; Leibach, F. H.; Ganapathy, V. cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem. Biophys. Res. Commun. 1998, 246, 589-595.
22. Ohashi, R.; Tamai, I.; Yabuuchi, H.; Nezu, J. I.; Oku, A.; Sai, Y.; Shimane, M.; Tsuji, A. Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J. Pharmacol. Exp. Ther. 1999, 291, 778-784.
23. Campistol, J.; Chavez, B.; Vilaseca, M. A.; Artuch, R. [Antiepileptic drugs and carnitine]. Rev. Neurol. 2000, 30 (Suppl. 1), S105-S109.
24. Tein, I.; DiMauro, S.; Xie, Z. W.; De Vivo, D. C. Valproic acid impairs carnitine uptake in cultured human skin fibroblasts. An in vitro model for the pathogenesis of valproic acid-associated carnitine deficiency. Pediatr. Res. 1993, 34, 281-287.
25. Berezowski, V.; Miecz, D.; Marszalek, M.; Broer, A.; Broer, S.; Cecchelli, R.; Nalecz, K. A. Involvement of OCTN2 and B0,+ in the transport of carnitine through an in vitro model of the bloodbrain barrier. J. Neurochem. 2004, 91, 860-872.
26. Lamhonwah, A. M.; Skaug, J.; Scherer, S. W.; Tein, I. A third human carnitine/organic cation transporter (OCTN3) as a candidate for the 5q31 Crohn's disease locus (IBD5). Biochem. Biophys. Res. Commun. 2003, 301, 98-101.