Identification and pathway mapping of furan target proteins reveal mitochondrial energy production and redox regulation as critical targets of furan toxicity

Toxicological Sciences

Volumn 126, Issue 2, 2012, Pages 336-352

  Moro, Sabrina ^a   Chipman, J Kevin ^b   Antczak, Philipp ^b   Turan, Nil ^b   Dekant, Wolfgang ^a   Falciani, Francesco ^b   Mally, Angela ^a  

^a UNIVERSITY OF WÜRZBURG   (Germany)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

Author keywords

Carcinogenicity; Furan; Liver; Protein adducts

Indexed keywords

ADENOSINE TRIPHOSPHATE; CARBON 14; FURAN; LIVER PROTEIN; MITOCHONDRIAL ENZYME; STRUCTURAL PROTEIN; TRYPSIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; CYTOSOL; ENERGY YIELD; FATTY ACID OXIDATION; FLUOROGRAPHY; GLUCOSE METABOLISM; HOMEOSTASIS; ISOTOPE LABELING; LIVER CARCINOGENESIS; LIVER TOXICITY; LONG TERM EXPOSURE; MALE; MASS SPECTROMETRY; MITOCHONDRION; NONHUMAN; PROTEIN FOLDING; PROTEIN LOCALIZATION; RAT; TWO DIMENSIONAL GEL ELECTROPHORESIS;

ANIMALIA; RATTUS; RODENTIA;

EID: 84859085369     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfs005     Document Type: Article

References (78)

1. Abu-Hamad, S., Sivan, S., and Shoshan-Barmatz, V. (2006). The expression level of the voltage-dependent anion channel controls life and death of the cell. Proc. Natl. Acad. Sci. U.S.A. 103, 5787-5792.
2. Alchi, B., Nishi, S., Kondo, D., Kaneko, Y., Matsuki, A., Imai, N., Ueno, M., Iguchi, S., Sakatsume, M., Narita, I., et al. (2005). Osteopontin expression in acute renal allograft rejection. Kidney Int. 67, 886-896.
3. Anderson, N. L., Esquer-Blasco, R., Hofmann, J. P., and Anderson, N. G. (1991). A two-dimensional gel database of rat liver proteins useful in gene regulation and drug effects studies. Electrophoresis 12, 907-930.
4. Anderson, N. L., Esquer-Blasco, R., Hofmann, J. P., Meheus, L., Raymackers, J., Steiner, S., Witzmann, F., and Anderson, N. G. (1995). An updated two-dimensional gel database of rat liver proteins useful in gene regulation and drug effect studies. Electrophoresis 16, 1977-1981.
5. Asif, A. R., Armstrong, V. W., Voland, A., Wieland, E., Oellerich, M., and Shipkova, M. (2007). Proteins identified as targets of the acyl glucuronide metabolite of mycophenolic acid in kidney tissue from mycophenolate mofetil treated rats. Biochimie 89, 393-402.
6. Bourdi, M., Chen, W., Peter, R. M., Martin, J. L., Buters, J. T., Nelson, S. D., and Pohl, L. R. (1996). Human cytochrome P450 2E1 is a major autoantigen associated with halothane hepatitis. Chem. Res. Toxicol. 9, 1159-1166.
7. Brisson, D., Vohl, M. C., St-Pierre, J., Hudson, T. J., and Gaudet, D. (2001). Glycerol: A neglected variable in metabolic processes? Bioessays 23, 534-542.
8. Burka, L. T., Washburn, K. D., and Irwin, R. D. (1991). Disposition of [14C]furan in the male F344 rat. J. Toxicol. Environ. Health 34, 245-257.
9. Byrns, M. C., Predecki, D. P., and Peterson, L. A. (2002). Characterization of nucleoside adducts of cis-2-butene-1,4-dial, a reactive metabolite of furan. Chem. Res. Toxicol. 15, 373-379.
10. Byrns, M. C., Vu, C. C., and Peterson, L. A. (2004). The formation of substituted 1, N6-etheno-2'-deoxyadenosine and 1, N2-etheno-2'-deoxyguanosine adducts by cis-2-butene-1,4-dial, a reactive metabolite of furan. Chem. Res. Toxicol. 17, 1607-1613.
11. Chen, L. J., Hecht, S. S., and Peterson, L. A. (1997). Characterization of amino acid and glutathione adducts of cis-2-butene-1,4-dial, a reactive metabolite of furan. Chem. Res. Toxicol. 10, 866-874.
12. Chen, T., Mally, A., Ozden, S., and Chipman, J. K. (2010). Low doses of the carcinogen furan alter cell cycle and apoptosis gene expression in rat liver independent of DNA methylation. Environ. Health Perspect. 118, 1597-1602.
13. Cohen, S. D., Pumford, N. R., Khairallah, E. A., Boekelheide, K., Pohl, L. R., Amouzadeh, H. R., and Hinson, J. A. (1997). Selective protein covalent binding and target organ toxicity. Toxicol. Appl. Pharmacol. 143, 1-12.
14. Crabb, D. W., Matsumoto, M., Chang, D., and You, M. (2004). Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc. Nutr. Soc. 63, 49-63.
15. Crews, C., and Castle, L. (2007). A review of the occurrence, formation and analysis of furan in heat-processed foods. Trends Food Sci. Technol. 18, 365-372.
16. Dennis, G., Jr, Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., and Lempicki, R. A. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 4, P3.
17. Dooley, G. P., Reardon, K. F., Prenni, J. E., Tjalkens, R. B., Legare, M. E., Foradori, C. D., Tessari, J. E., and Hanneman, W. H. (2008). Proteomic analysis of diaminochlorotriazine adducts in Wistar rat pituitary glands and LbetaT2 rat pituitary cells. Chem. Res. Toxicol. 21, 844-851.
18. Dowsley, T. F., Reid, K., Petsikas, D., Ulreich, J. B., Fisher, R. L., and Forkert, P. G. (1999). Cytochrome P-450-dependent bioactivation of 1,1-dichloroethylene to a reactive epoxide in human lung and liver microsomes. J. Pharmacol. Exp. Ther. 289, 641-648.
19. Druckova, A., Mernaugh, R. L., Ham, A. J., and Marnett, L. J. (2007). Identification of the protein targets of the reactive metabolite of teucrin A in vivo in the rat. Chem. Res. Toxicol. 20, 1393-1408.
20. Evans, D. C., Watt, A. P., Nicoll-Griffith, D. A., and Baillie, T. A. (2004). Drug-protein adducts: An industry perspective on minimizing the potential for drug bioactivation in drug discovery and development. Chem. Res. Toxicol. 17, 3-16.
21. Fairbanks, K. D., and Tavill, A. S. (2008). Liver disease in alpha 1-antitrypsin deficiency: A review. Am. J. Gastroenterol. 103, 2136-2141; quiz 2142.
22. Fang, J., Koen, Y. M., and Hanzlik, R. P. (2009). Bioinformatic analysis of xenobiotic reactive metabolite target proteins and their interacting partners. BMC Chem. Biol. 9, 5.
23. Galeva, N., and Altermann, M. (2002). Comparison of one-dimensional and two-dimensional gel electrophoresis as a separation tool for proteomic analysis of rat liver microsomes: Cytochromes P450 and other membrane proteins. Proteomics 2, 713-722.
24. Gill, S., Bondy, G., Lefebvre, D. E., Becalski, A., Kavanagh, M., Hou, Y., Turcotte, A. M., Barker, M., Weld, M., Vavasour, E., et al. (2010). Subchronic oral toxicity study of furan in Fischer-344 rats. Toxicol. Pathol. 38, 619-630.
25. Gut, I., Nedelcheva, V., Soucek, P., Stopka, P., and Tichavska, B. (1996). Cytochromes P450 in benzene metabolism and involvement of their metabolites and reactive oxygen species in toxicity. Environ. Health Perspect. 104(Suppl. 6), 1211-1218.
26. Hamberger, C., Kellert, M., Schauer, U. M., Dekant, W., and Mally, A. (2010). Hepatobiliary toxicity of furan: Identification of furan metabolites in bile of male F344/N rats. Drug Metab. Dispos. 38, 1698-1706.
27. Hanzlik, R. P., Fang, J., and Koen, Y. M. (2009). Filling and mining the reactive metabolite target protein database. Chem. Biol. Interact. 179, 38-44.
28. Hickling, K., Hitchcock, J. M., Chipman, J. K., Hammond, T. G., and Evans, J. G. (2010a). Induction and progression of cholangiofibrosis in rat liver injured by oral administration of furan. Toxicol. Pathol. 38, 213-229.
29. Hickling, K. C., Hitchcock, J. M., Oreffo, V., Mally, A., Coleman, R., Hammond, T. G., Evans, J. G., and Chipman, J. K. (2010b). Evidence of oxidative stress and associated DNA damage, increased proliferative drive and altered gene expression in rat liver produced by the cholangiocarcinogenic agent furan. Toxicol. Pathol. 38, 230-243.
30. Hoivik, D. J., Manautou, J. E., Tveit, A., Mankowski, D. C., Khairallah, E. A., and Cohen, S. D. (1996). Evidence suggesting the 58-kDa acetaminophen binding protein is a preferential target for acetaminophen electrophile. Fundam. Appl. Toxicol. 32, 79-86.
31. Huang, Q., Jin, X., Gaillard, E. T., Knight, B. L., Pack, F. D., Stoltz, J. H., Jayadev, S., and Blanchard, K. T. (2004). Gene expression profiling reveals multiple toxicity endpoints induced by hepatotoxicants. Mutat. Res. 549, 147-167.
32. Huang da, W., Sherman, B. T., and Lempicki, R. A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57.
33. Ikehata, K., Duzhak, T. G., Galeva, N. A., Ji, T., Koen, Y. M., and Hanzlik, R. P. (2008). Protein targets of reactive metabolites of thiobenzamide in rat liver in vivo. Chem. Res. Toxicol. 21, 1432-1442.
34. Ishii, T., Tatsuda, E., Kumazawa, S., Nakayama, T., and Uchida, K. (2003). Molecular basis of enzyme inactivation by an endogenous electrophile 4-hydroxy-2-nonenal: Identification of modification sites in glyceraldehyde-3-phosphate dehydrogenase. Biochemistry 42, 3474-3480.
35. Kalinina, E. V., Chernov, N. N., and Saprin, A. N. (2008). Involvement of thio-, peroxi-, and glutaredoxins in cellular redox-dependent processes. Biochemistry (Mosc.) 73, 1493-1510.
36. Kedderis, G. L., Batra, R., and Koop, D. R. (1993). Epoxidation of acrylonitrile by rat and human cytochromes P450. Chem. Res. Toxicol. 6, 866-871.
37. Kellert, M., Wagner, S., Lutz, U., and Lutz, W. K. (2008). Biomarkers of furan exposure by metabolic profiling of rat urine with liquid chromatographytandem mass spectrometry and principal component analysis. Chem. Res. Toxicol. 21, 761-768.
38. Kim, A., Kim, M. J., Yang, Y., Kim, J. W., Yeom, Y. I., and Lim, J. S. (2009a). Suppression of NF-kappaB activity by NDRG2 expression attenuates the invasive potential of highly malignant tumor cells. Carcinogenesis 30, 927-936.
39. Kim, Y. J., Yoon, S. Y., Kim, J. T., Choi, S. C., Lim, J. S., Kim, J. H., Song, E. Y., Lee, H. G., Choi, I., and Kim, J. W. (2009b). NDRG2 suppresses cell proliferation through down-regulation of AP-1 activity in human colon carcinoma cells. Int. J. Cancer 124, 7-15.
40. Klouckova, I., Hrncirova, P., Mechref, Y., Arnold, R. J., Li, T. K., McBride, W. J., and Novotny, M. V. (2006). Changes in liver protein abundance in inbred alcohol-preferring rats due to chronic alcohol exposure, as measured through a proteomics approach. Proteomics 6, 3060-3074.
41. Koen, Y. M., Gogichaeva, N. V., Alterman, M. A., and Hanzlik, R. P. (2007). A proteomic analysis of bromobenzene reactive metabolite targets in rat liver cytosol in vivo. Chem. Res. Toxicol. 20, 511-519.
42. Koen, Y. M., and Hanzlik, R. P. (2002). Identification of seven proteins in the endoplasmic reticulum as targets for reactive metabolites of bromobenzene. Chem. Res. Toxicol. 15, 699-706.
43. Kurebayashi, H., and Ohno, Y. (2006). Metabolism of acrylamide to glycidamide and their cytotoxicity in isolated rat hepatocytes: Protective effects of GSH precursors. Arch. Toxicol. 80, 820-828.
44. Labenski, M. T., Fisher, A. A., Lo, H. H., Monks, T. J., and Lau, S. S. (2009). Protein electrophile-binding motifs: Lysine-rich proteins are preferential targets of quinones. Drug Metab. Dispos. 37, 1211-1218.
45. Laine, J. E., Auriola, S., Pasanen, M., and Juvonen, R. O. (2009). Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica 39, 11-21.
46. Lauriault, V. V., Khan, S., and O'Brien, P. J. (1992). Hepatocyte cytotoxicity induced by various hepatotoxins mediated by cytochrome P-450IIE1: Protection with diethyldithiocarbamate administration. Chem. Biol. Interact. 81, 271-289.
47. Lawen, A., Ly, J. D., Lane, D. J., Zarschler, K., Messina, A., and De Pinto, V. (2005). Voltage-dependent anion-selective channel 1 (VDAC1)-a mitochondrial protein, rediscovered as a novel enzyme in the plasma membrane. Int. J. Biochem. Cell Biol. 37, 277-282.
48. Lee, D. C., Kang, Y. K., Kim, W. H., Jang, Y. J., Kim, D. J., Park, I. Y., Sohn, B. H., Sohn, H. A., Lee, H. G., Lim, J. S., et al. (2008). Functional and clinical evidence for NDRG2 as a candidate suppressor of liver cancer metastasis. Cancer Res. 68, 4210-4220.
49. Lee, S. M., Kim, J. H., Cho, E. J., and Youn, H. D. (2009). A nucleocytoplasmic malate dehydrogenase regulates p53 transcriptional activity in response to metabolic stress. Cell Death Differ. 16, 738-748.
50. Low, T. Y., Leow, C. K., Salto-Tellez, M., and Chung, M. C. (2004). A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers. Proteomics 4, 3960-3974.
51. Lu, D., and Peterson, L. A. (2010). Identification of furan metabolites derived from cysteine-cis-2-butene-1,4-dial-lysine cross-links. Chem. Res. Toxicol. 23, 142-151.
52. Lu, D., Sullivan, M. M., Phillips, M. B., and Peterson, L. A. (2009). Degraded protein adducts of cis-2-butene-1,4-dial are urinary and hepatocyte metabolites of furan. Chem. Res. Toxicol. 22, 997-1007.
53. Lu, S. C., Alvarez, L., Huang, Z. Z., Chen, L., An, W., Corrales, F. J., Avila, M. A., Kanel, G., and Mato, J. M. (2001). Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc. Natl. Acad. Sci. U.S.A. 98, 5560-5565.
54. Mally, A., Graff, C., Schmal, O., Moro, S., Hamberger, C., Schauer, U. M., Bruck, J., Ozden, S., Sieber, M., Steger, U., et al. (2010). Functional and proliferative effects of repeated low-dose oral administration of furan in rat liver. Mol. Nutr. Food Res. 54, 1556-1567.
55. Marcinowski, M., Holler, M., Feige, M. J., Baerend, D., Lamb, D. C., and Buchner, J. (2011). Substrate discrimination of the chaperone BiP by autonomous and cochaperone-regulated conformational transitions. Nat. Struct. Mol. Biol. 18, 150-158.
56. Martin, S., Hill, D. S., Paton, J. C., Paton, A. W., Birch-Machin, M. A., Lovat, P. E., and Redfern, C. P. (2010). Targeting GRP78 to enhance melanoma cell death. Pigment Cell Melanoma Res. 23, 675-682.
57. Martinez-Chantar, M. L., Corrales, F. J., Martinez-Cruz, L. A., Garcia-Trevijano, E. R., Huang, Z. Z., Chen, L., Kanel, G., Avila, M. A., Mato, J. M., and Lu, S. C. (2002). Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A. FASEB J. 16, 1292-1294.
58. Minarik, P., Tomaskova, N., Kollarova, M., and Antalik, M. (2002). Malate dehydrogenases-structure and function. Gen. Physiol. Biophys. 21, 257-265.
59. Miseta, A., and Csutora, P. (2000). Relationship between the occurrence of cysteine in proteins and the complexity of organisms. Mol. Biol. Evol. 17, 1232-1239.
60. Mugford, C. A., Carfagna, M. A., and Kedderis, G. L. (1997). Furan-mediated uncoupling of hepatic oxidative phosphorylation in Fischer-344 rats: An early event in cell death. Toxicol. Appl. Pharmacol. 144, 1-11.
61. National Toxicology Program (NTP). (1993). Toxicology and carcinogenesis studies of furan (CAS No. 110-00-9) in F344 rats and B6C3F1 mice (gavage studies). Natl. Toxicol. Program Tech. Rep. Ser. 402, 1-286.
62. Pancholi, V. (2001). Multifunctional alpha-enolase: Its role in diseases. Cell. Mol. Life Sci. 58, 902-920.
63. Patel, J., Pathak, R. R., and Mujtaba, S. (2011). The biology of lysine acetylation integrates transcriptional programming and metabolism. Nutr. Metab. (Lond.) 8, 12.
64. Powis, G., and Montfort, W. R. (2001). Properties and biological activities of thioredoxins. Annu. Rev. Pharmacol. Toxicol. 41, 261-295.
65. Qiu, Y., Benet, L. Z., and Burlingame, A. L. (1998). Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry. J. Biol. Chem. 273, 17940-17953.
66. Samali, A., Fitzgerald, U., Deegan, S., and Gupta, S. (2010). Methods for monitoring endoplasmic reticulum stress and the unfolded protein response. Int. J. Cell Biol. 2010, 830307.
67. Shoshan-Barmatz, V., De Pinto, V., Zweckstetter, M., Raviv, Z., Keinan, N., and Arbel, N. (2010). VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol. Aspects Med. 31, 227-285.
68. Son, T. G., Zou, Y., Jung, K. J., Yu, B. P., Ishigami, A., Maruyama, N., and Lee, J. (2006). SMP30 deficiency causes increased oxidative stress in brain. Mech. Ageing Dev. 127, 451-457.
69. Takikawa, H., Sugiyama, Y., Fernandez-Checa, J. C., Kuhlenkamp, J., Ookhtens, M., and Kaplowitz, N. (1996). Evidence that interference with binding to hepatic cytosol binders can inhibit bile acid excretion in rats. Hepatology 23, 1642-1649.
70. Usui, E., Okuda, K., Kato, Y., and Noshiro, M. (1994). Rat hepatic 3 alpha-hydroxysteroid dehydrogenase: Expression of cDNA and physiological function in bile acid biosynthetic pathway. J. Biochem. 115, 230-237.
71. Van Molle, W., Libert, C., Fiers, W., and Brouckaert, P. (1997). Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice. J. Immunol. 159, 3555-3564.
72. Wenzel, P., Muller, J., Zurmeyer, S., Schuhmacher, S., Schulz, E., Oelze, M., Pautz, A., Kawamoto, T., Wojnowski, L., Kleinert, H., et al. (2008). ALDH-2 deficiency increases cardiovascular oxidative stress-evidence for indirect antioxidative properties. Biochem. Biophys. Res. Commun. 367, 137-143.
73. Wilson, D. M., Goldsworthy, T. L., Popp, J. A., and Butterworth, B. E. (1992). Evaluation of genotoxicity, pathological lesions, and cell proliferation in livers of rats and mice treated with furan. Environ. Mol. Mutagen. 19, 209-222.
74. Yamaguchi, M. (2000). Role of regucalcin in calcium signaling. Life Sci. 66, 1769-1780.
75. Zhang, B., Abreu, J. G., Zhou, K., Chen, Y., Hu, Y., Zhou, T., He, X., and Ma, J. X. (2010). Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family. Proc. Natl. Acad. Sci. U.S.A. 107, 6900-6905.
76. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2011). Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000-1004.
77. Zhou, S. (2003). Separation and detection methods for covalent drug-protein adducts. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 797, 63-90.
78. Zhou, S., Chan, E., Duan, W., Huang, M., and Chen, Y. Z. (2005). Drug bioactivation, covalent binding to target proteins and toxicity relevance. Drug Metab. Rev. 37, 41-213.