Circumventing the crabtree effect: Replacing media glucose with galactose increases susceptibility of hepG2 cells to mitochondrial toxicants

Toxicological Sciences

Volumn 97, Issue 2, 2007, Pages 539-547

  Marroquin, Lisa D ^a   Hynes, James ^b   Dykens, James A ^a   Jamieson, Joseph D ^a   Will, Yvonne ^a  

^a PFIZER INC   (United States)

^b UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

Drug safety testing; HepG2 cells; Mitochondria; OXPHOS; Respiration

Indexed keywords

BICALUTAMIDE; CITRININ; DOXORUBICIN; FENOFIBRATE; FLUTAMIDE; GALACTOSE; GLUCOSE; IMIPRAMINE; NEFAZODONE; NIMODIPINE; OLIGOMYCIN; RISPERIDONE; ROTENONE; TAMOXIFEN;

ARTICLE; CELL ASSAY; CELL COUNT; CELL CULTURE; CELL STRAIN HEPG2; CELL VIABILITY; CONTROLLED STUDY; CULTURE MEDIUM; DRUG CYTOTOXICITY; GLYCOLYSIS; HUMAN; HUMAN CELL; MITOCHONDRIAL TOXICITY; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION;

ADENOSINE TRIPHOSPHATE; CELL COUNT; CELL LINE; CULTURE MEDIA; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; GALACTOSE; GLUCOSE; GLYCOLYSIS; HUMANS; MITOCHONDRIA, LIVER; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION; TOXICITY TESTS; UNCOUPLING AGENTS;

EID: 34447577912     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfm052     Document Type: Article

References (40)

1. Amacher, D. E. (2005). Drug-associated mitochondrial toxicity and its detection. Curr. Med. Chem. 12, 1829-1839.
2. Berger, W., Mehnert-Aner, S., Mully, K., Heierli, C., and Ritz, R. (1976). Ten cases of lactic acidosis during biguanide therapy (buformin and phenformin). Schweiz. Med. Wochenschr. 106, 1830-1834.
3. Brunmair, B., Staniek, K., Gras, F., Scharf,N., Althaym, A., Clara, R., Roden,M., Gnaiger, E., Nohl, H., Waldhäusl, W., et al. (2004). Thiazolidinediones, like metformin, inhibit respiratory complex I. Diabetes 53, 1052-1059.
4. Cardoso, C., Custodio, J., Almeida, L., and Moreno, A. (2001). Mechanisms of the deleterious effects of Tamoxifen on mitochondrial respiration rate and phosphorylation efficiency. Toxicol. Appl. Pharmacol. 176, 145-152.
5. Chan, K., Truong, D., Shangari, N., and O'Brien, P. J. (2005). Drug-induced mitochondrial toxicity. Expert Opin. Drug Metab. Toxicol. 1, 655-669.
6. Cote, H. C., Magil, A. B., Harris, M., Scarth, B. J., Gadawski, I., Wang, N., Yu, E., Yip, B., Zalunardo, N.,Werb, R., et al. (2006). Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy. Antivir. Ther. 11, 79-86.
7. Cruz Silva, M. M., Madeira, V. M., Almeida, L. M., and Custodio, J. B. (2000). Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure. Biochim. Biophys. Acta. 1464, 49-61.
8. Dawson, L. A., Chow, E., and Morton, G. (1997). Fulminant hepatic failure associated with bicalutamide. Urology 49, 283-284.
9. Duzenli, S., Bakuridze, K., and Gepdiremen, A. (2005). The effects of ruthenium red, dantrolene and nimodipine, alone or in combination, in NMDA induced neurotoxicity of cerebellar granular cell culture of rats. Toxicol. In Vitro 19, 589-594.
10. Dykens, J. A., Marroquin, L. andWill, Y. (2007). Strategies to reduce late stage drug attrition due to mitochondrial toxicity: Development of a high throughput respiration screen. Expert Opin. Mol. Diagn. 7, 161-175.
11. Eyles, D. W., Pond, S. M., Van der Schyf, C. J., and Halliday, G. M. (2000). Mitochondrial ultrastructure and density in a primate model of persistent tardive dyskinesia. Life Sci. 66, 1345-1350.
12. Fau, D., Eugene, D., Berson, A., Letteron, P., Fromenty, B., Fisch, C., and Pessayre, D. (1994). Toxicity of the antiandrogen flutamide in isolated rat hepatocytes. J. Pharmacol. Exp. Ther. 269, 954-962.
13. Gille, L., and Nohl, H. (1997). Analysis of the molecular mechanism of adriamycin-induced cardiotoxicity. Free Radic. Biol. Med. 23 775-782.
14. Golshani-Hebroni, S. G., and Bessman, S. P. (1997). Hexokinase binding to mitochondria: A basis for proliferative energy metabolism. J. Bioenerg. Biomembr. 29, 331-338.
15. Gomez, J. L., Dupont, A., Cusan, L., Tremblay, M., Suburu, R., Lemay, M., and Labrie, F. (1992). Incidence of liver toxicity associated with the use of flutamide in prostate cancer patients. Pharmacol. Ther. 92, 465-470.
16. Hynes, J., Marroquin, L., Ogurtsov, V., Christiansen, K., Stevens, G., Papkovsky, D., and Will, Y. (2006). Investigation of drug-induced mitochondrial toxicity using fluorescence-based oxygen-sensitive probes. Toxicol. Sci. 92, 186-200.
17. Katyare, S. S., and Rajan, R. R. (1995). Effect of long-term in vivo treatment with imipramine on the oxidative energy metabolism in rat brain mitochondria. Pharmacol. Toxicol. Endocrinol. 112, 353-357.
18. Kaufmann, P., Torok, M., Zahno, A., Waldhauser, K. M., Brecht, K., and Krahenbuhl, S. (2006). Toxicity of statins on rat skeletal muscle mitochondria. Cell Mol. Life Sci. 63, 2415-2425.
19. Krebs, S., Dormann, H., Muth-Selbach, U., Hahn, E. G., Brune, K., and Schneider, H. T. (2001). Risperidone-induced cholestatic hepatitis. Eur. J. Gastroenterol. Hepatol. 13, 67-69.
20. Lin, Y., Kokontis, J., Tang, F., Godfrey, B., Liao, S., Lin, A., Chen, Y., and Xiang, J. (2006). Androgen and its receptor promote Bax-mediated apoptosis. Mol. Cell. Biol. 26, 1908-1916.
21. Malhi, H., Gores, G. J., and Lemasters, J. J. (2006). Apoptosis and necrosis in the liver: A tale of two deaths. Hepatology 43, S31-S44.
22. Masubuchi, Y., Kano, S., and Horie, T. (2006). Mitochondrial permeability transition as a potential determinant of hepatotoxicity of antidiabetic thiazolidinediones. Toxicology 222, 233-239.
23. McKee, E. E., Ferguson, M., Bentley, A. T., and Marks, T. A. (2006). Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob. Agents Chemother. 50, 2042-2049.
24. Modica-Napolitano, J. S., Lagace, C. J., Brennan, W. A., and Aprille, J. R. (2003). Differential effects of typical neuroleptics on mitochondrial function in vitro. Arch. Pharm. Res. 26, 951-959.
25. Moring, J., Shoemaker, W. J., Skita, V., Mason, R. P., Hayden, H. C., Salomon, R. M., and Herbette, L. G. (1990). Rat cerebral cortical synaptoneurosomal membranes. Structure and interactions with imidazobenzodiazepine and 1,4-dihydropyridine calcium channel drugs. Biophys. J. 58, 513-531.
26. Nadanaciva, S., Bernal, A., Aggeler, R., Capaldi, R., andWill, Y. (2007). Target Identification of drug induced mitochondria toxicity using monoclonal antibody capture OXPHOS activity assays. Toxicol. In Vitro (in press).
27. Ong, M. M., Latchoumycandane, C., and Boelsterli, U. A. (2007). Troglitazone-induced hepatic necrosis in an animal model of silent genetic mitochondrial abnormalities. Toxicol. Sci. 97(1), 205-213.
28. 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, 607-614.
29. Pacher, P., and Kecskemeti, V. (2004). Cardiovascular side effects of new antidepressants and antipsychotics: New drugs, old concerns? Curr. Pharm. Des. 10, 2463-2475.
30. Palmero, M., Gutierrez, L. M., Hidalgo, M. J., Reig, J. A., Ballesta, J. J., and Viniegra, S. (1995). The low-affinity dihydropyridine receptor and Na+/Ca2+ exchanger are associated in adrenal medullary mitochondria. Biochem. Pharmacol. 50, 879-883.
31. Rodríguez-Enríquez, S., Juárez, O., Rodríguez-Zavala, J. S., and Moreno-Sánchez, R. (2001). Multisite control of the Crabtree effect in ascites hepatoma cells. Eur. J. Biochem. 268, 2512-2519.
32. Rodriguez y Baena, R., Gaetani, P., Silvani, V., Spanu, G., and Marzatico, F. (1988). Effect of nimodipine on mitochondrial respiration in different rat brain areas after subarachnoid haemorrhage. Microb. Agents Chemother. 43, 177-181.
33. Rossignol, R., Gilkerson, R., Aggeler, R., Yamagata, K., James Remington, S., and Capaldi, R. A. (2004). Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res. 64, 985-993.
34. Scatena, R., Bottoni, P., Matorana, G. E., Ferrari, F., De Sole, P., Rossi, C., and Giardina, B. (2004). Mitochondrial respiratory chain dysfunction, a non receptor-mediated effect of syntetic PPAR-ligands. Biochemical and pharmacological implications. Biochem. Biophys. Res. Commun. 319, 967-973.
35. Schaefer,W. H., Lawrence, J.W., Loughlin, A. F., Stoffregen, D. A., Mixson, L. A., Dean, D. C., Raab, C. E., Yu, N. X., Lankas, G. R., and Frederick, C. B. (2004). Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats. Toxicol. App. Pharmacol. 194, 10-23.
36. Scheffler, I. (1999). Mitochondria, 1st ed., pp. 367. John Wiley, New York.
37. Vignati, L., Turlizzi, E., Monaci, S., Grossi, P., Kanter, R., and Monshouwer, M. (2005). An in vitro approach to detect metabolite toxicity due to CYP3A4-dependent bioactivation of xenobiotics. Toxicology 216, 154-167.
38. Wallace, K. B., and Starkov, A. A. (2000). Mitochondrial targets of drug toxicity. Annu. Rev. Pharmacol. Toxicol. 40, 353-388.
39. Warburg, O., Geissler, A. W., and Lorenz, S. (1967). On growth of cancer cells in media in which glucose is replaced by galactose. Hoppe Seylers Z. Physiol. Chem. 348, 1686-1687.
40. Wilkening, S., Stahl, F., and Bader, A. (2003). Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties. Drug Metab. Dispos. 31, 1035-1042.