Role of organic cation/carnitine transporter 1 in uptake of phenformin and inhibitory effect on complex i respiration in mitochondria

Toxicological Sciences

Volumn 132, Issue 1, 2013, Pages 32-42

  Shitara, Yoshihisa ^a,c   Nakamichi, Noritaka ^b   Norioka, Misaki ^a   Shima, Hiroyo ^b   Kato, Yukio ^b   Horie, Toshiharu ^a  

^a CHIBA UNIVERSITY   (Japan)

^b KANAZAWA UNIVERSITY   (Japan)

^c MEIJI SEIKA KAISHA LTD   (Japan)

Author keywords

Lactic acidosis; Mitochondria; Octn1; Phenformin; Uptake

Indexed keywords

LACTIC ACID; ORGANIC CATION TRANSPORTER 1; PHENFORMIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE);

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOACCUMULATION; CELL STRAIN HEK293; COMPETITIVE INHIBITION; CONTROLLED STUDY; HEART MITOCHONDRION; HUMAN; HUMAN CELL; ISOLATED LIVER; LACTATE BLOOD LEVEL; LACTIC ACIDOSIS; LIVER MITOCHONDRION; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; OXYGEN CONSUMPTION; PROTEIN EXPRESSION; PROTEIN FUNCTION; RAT; WILD TYPE;

ANIMALS; CARNITINE; ELECTRON TRANSPORT COMPLEX I; HEK293 CELLS; HUMANS; MICE; MITOCHONDRIA, HEART; ORGANIC CATION TRANSPORTER 1; OXYGEN CONSUMPTION; PHENFORMIN; RATS;

MUS; RATTUS; RODENTIA;

EID: 84876488863     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfs330     Document Type: Article

References (32)

1. Bailey, C. J. (1992). Biguanides and NIDDM. Diabetes Care 15, 755-772.
2. Bailey, C. J., and Turner, R. C. (1996). Metformin. N. Engl. J. Med. 334, 574-579.
3. Berger, W. (1985). Incidence of severe side effects during therapy with sulfonylureas and biguanides. Horm. Metab. Res. Suppl. 15, 111-115.
4. Chen, Y., Li, S., Brown, C., Cheatham, S., Castro, R. A., Leabman, M. K., Urban, T. J., Chen, L., Yee, S. W., Choi, J. H., et al. (2009). Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin. Pharmacogenet. Genomics 19, 497-504.
5. Davidoff, F. (1971). Effects of guanidine derivatives on mitochondrial function. 3. The mechanism of phenethylbiguanide accumulation and its relationship to in vitro respiratory inhibition. J. Biol. Chem. 246, 4017-4027.
6. DeFronzo, R. A., and Goodman, A. M. (1995). Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N. Engl. J. Med. 333, 541-549.
7. Jungsuwadee, P., Nithipongvanitch, R., Chen, Y., Oberley, T. D., Butterfield, D. A., St Clair, D. K., and Vore, M. (2009). Mrp1 localization and function in cardiac mitochondria after doxorubicin. Mol. Pharmacol. 75, 1117-1126.
8. Kato, Y., Kubo, Y., Iwata, D., Kato, S., Sudo, T., Sugiura, T., Kagaya, T., Wakayama, T., Hirayama, A., Sugimoto, M., et al. (2010). Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm. Res. 27, 832-840.
9. Kimura, N., Masuda, S., Tanihara, Y., Ueo, H., Okuda, M., Katsura, T., and Inui, K. (2005a). Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. Drug Metab. Pharmacokinet. 20, 379-386.
10. Kimura, N., Okuda, M., and Inui, K. (2005b). Metformin transport by renal basolateral organic cation transporter hOCT2. Pharm. Res. 22, 255-259.
11. Lai, Y., Tse, C. M., and Unadkat, J. D. (2004). Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs. J. Biol. Chem. 279, 4490-4497.
12. Lamhonwah, A. M., and Tein, I. (2006). Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria. Biochem. Biophys. Res. Commun. 345, 1315-1325.
13. Lee, E. W., Lai, Y., Zhang, H., and Unadkat, J. D. (2006). Identification of the mitochondrial targeting signal of the human equilibrative nucleoside transporter 1 (hENT1): Implications for interspecies differences in mitochondrial toxicity of fialuridine. J. Biol. Chem. 281, 16700-16706.
14. Masuda, S., Terada, T., Yonezawa, A., Tanihara, Y., Kishimoto, K., Katsura, T., Ogawa, O., and Inui, K. (2006). Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J. Am. Soc. Nephrol. 17, 2127-2135.
15. Misbin, R. I. (1977). Phenformin-associated lactic acidosis: Pathogenesis and treatment. Ann. Intern. Med. 87, 591-595.
16. Misbin, R. I., Green, L., Stadel, B. V., Gueriguian, J. L., Gubbi, A., and Fleming, G. A. (1998). Lactic acidosis in patients with diabetes treated with metformin. N. Engl. J. Med. 338, 265-266.
17. Okuda, T., Norioka, M., Shitara, Y., and Horie, T. (2010). Multiple mechanisms underlying troglitazone-induced mitochondrial permeability transition. Toxicol. Appl. Pharmacol. 248, 242-248.
18. Owen, M. R., Doran, E., and Halestrap, A. P. (2000). Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348(Pt 3), 607-614.
19. Shu, Y., Brown, C., Castro, R. A., Shi, R. J., Lin, E. T., Owen, R. P., Sheardown, S. A., Yue, L., Burchard, E. G., Brett, C. M., et al. (2008). Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin. Pharmacol. Ther. 83, 273-280.
20. Shu, Y., Sheardown, S. A., Brown, C., Owen, R. P., Zhang, S., Castro, R. A., Ianculescu, A. G., Yue, L., Lo, J. C., Burchard, E. G., et al. (2007). Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J. Clin. Invest. 117, 1422-1431.
21. Song, I. S., Shin, H. J., Shim, E. J., Jung, I. S., Kim, W. Y., Shon, J. H., and Shin, J. G. (2008). Genetic variants of the organic cation transporter 2 influence the disposition of metformin. Clin. Pharmacol. Ther. 84, 559-562.
22. Stang, M., Wysowski, D. K., and Butler-Jones, D. (1999). Incidence of lactic acidosis in metformin users. Diabetes Care 22, 925-927.
23. Sugiura, T., Kato, S., Shimizu, T., Wakayama, T., Nakamichi, N., Kubo, Y., Iwata, D., Suzuki, K., Soga, T., Asano, M., et al. (2010). Functional expression of carnitine/organic cation transporter OCTN1/SLC22A4 in mouse small intestine and liver. Drug Metab. Dispos. 38, 1665-1672.
24. Tamai, I., Ohashi, R., Nezu, J. I., Sai, Y., Kobayashi, D., Oku, A., Shimane, M., and Tsuji, A. (2000). Molecular and functional characterization of organic cation/carnitine transporter family in mice. J. Biol. Chem. 275, 40064-40072.
25. Tamai, I., Yabuuchi, H., Nezu, J., Sai, Y., Oku, A., Shimane, M., and Tsuji, A. (1997). Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett. 419, 107-111.
26. Tanihara, Y., Masuda, S., Sato, T., Katsura, T., Ogawa, O., and Inui, K. (2007). Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem. Pharmacol. 74, 359-371.
27. Tzvetkov, M. V., Vormfelde, S. V., Balen, D., Meineke, I., Schmidt, T., Sehrt, D., Sabolić, I., Koepsell, H., and Brockmoller, J. (2009). The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin. Pharmacol. Ther. 86, 299-306.
28. Wang, D. S., Jonker, J. W., Kato, Y., Kusuhara, H., Schinkel, A. H., and Sugiyama, Y. (2002). Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. J. Pharmacol. Exp. Ther. 302, 510-515.
29. Wang, D. S., Kusuhara, H., Kato, Y., Jonker, J. W., Schinkel, A. H., and Sugiyama, Y. (2003). Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin. Mol. Pharmacol. 63, 844-848.
30. Wollen, N., and Bailey, C. J. (1988). Inhibition of hepatic gluconeogenesis by metformin. Synergism with insulin. Biochem. Pharmacol. 37, 4353-4358.
31. Wu, X., George, R. L., Huang, W., Wang, H., Conway, S. J., Leibach, F. H., and Ganapathy, V. (2000). Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim. Biophys. Acta 1466, 315-327.
32. Yabuuchi, H., Tamai, I., Nezu, J., Sakamoto, K., Oku, A., Shimane, M., Sai, Y., and Tsuji, A. (1999). Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J. Pharmacol. Exp. Ther. 289, 768-773.