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The mycotoxin fumonisin B1 inhibits eukaryotic protein synthesis: in vitro and in vivo studies

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Abstract

Inhibitory action of Fumonisin B1 (FB1) on eukaryotic protein synthesis was investigated, both in animal and plant system, and was compared with cycloheximide. Inhibitory effect of FB1 was monitored in the TCA precipitable proteins of rabbit reticulocyte lysates exposed to various concentrations of the mycotoxin (0.0013–2.76 mM), using 35 S-methionine as a tracer. FB1 inhibited the protein synthesis by 6%, at 0.0013 mM and by 88%, at a higher concentration of 2.76 mM. Cycloheximide at a concentration of 0.355 mM was found to inhibit protein synthesis by 88%. Inhibitory action of FB1 (1 mg kg−1 body mass and a higher dose of 10 mg kg−1 body mass) or cycloheximide (10 mg kg−1 body mass; positive controls), injected intra-peritoneally into BALB/c mice was studied using 14C-l-Leucine as a tracer. FB1 at lower dose of 1 mg kg−1 body mass inhibited protein synthesis in liver by 8% and at a higher dose of 10 mg kg−1 body mass by 38% in the BALB/c mice, when compared to cycloheximide which inhibited protein synthesis by 61%. The effects of FB1 on protein synthesis in plant system was studied in germinated maize seedlings exposed to FB1 at 0.9 µM, 0.009 mM and 0.09 mM concentrations, using 14C-l-Leucine as a tracer. Fumonisin B1 at low, middle, and higher concentrations (0.9 µM, 0.009 mM, and 0.09 mM) inhibited protein synthesis in the seedlings by 4%, 12% and 22%, respectively. The inhibitory effects of FB1 on the protein synthesis in the animal system in vitro and in vivo conditions, and in the plant system were found to be dose-dependent, though it was less potent compared to cycloheximide.

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Abbreviations

DPM:

Disintegrations per minute

FB1 :

Fumonisin B1

PPO:

2,5-diphenyloxazole

POPOP:

1,4-bis-2-(5-phenyloxazolyl)-benzene

RRL:

Rabbit reticulocyte lysate

TCA:

Trichloroacetic acid

References

  1. Gelderblom WCA, Jaskiewicz K, Marasas WFO, Thiel PG, Horak RM, Vleggaar R, Krik NPJ. Fumonisins—novel mycotoxins with cancer promoting activity produced by Fusarium moniliforme. Appl Environ Microbiol 1988; 54:1806–11.

    PubMed  CAS  Google Scholar 

  2. Bacon CW, Nelson PE. Fumonisin production in corn by toxigenic strains of Fusarium moniliforme and Fusarium proliferatum. J Food Protect 1994; 57:514–21.

    CAS  Google Scholar 

  3. Sydenham EW, Thiel PG, Marasas WFO, Shepherd GS, Van Schalkwyk DJ, Koch KR. Natural occurrence of some Fusarium mycotoxins in corn from low and high esophageal cancer prevalence areas of the Transkei, Southern Africa. J Agric Food Chem 1990; 38:1900–3.

    Article  CAS  Google Scholar 

  4. Yamashita T, Yoshizawa T, Aiura Y, Sanchez P, Diazon EI, Arim RH, Sardjono. Fusarium mycotoxins (fumonisins, nivalenol and zearalenone) and aflatoxin in corn from Southeast Asia. Biosci Biotechnol Biochem 1995; 59: 1804–7.

  5. Chatterji D, Mukherji SK. Contamination of Indian maize with Fumonisin B1 and its effects on chicken macrophage. Lett Appl Microbiol 1994; 18:251–3.

    Google Scholar 

  6. Shetty PH, Bhat RV. Natural occurrence of Fumonisin B1 and its co-occurrence with aflatoxin B1 in Indian sorghum, maize and poultry feeds. J Agric Food Chem 1997; 45:97–104.

    Article  Google Scholar 

  7. Marasas WFO. Fusarium moniliforme contamination of maize in oesophageal cancer areas in Transkei. S Afr Med J 1988; 94:110–4.

    Google Scholar 

  8. Harrison YA, Colvin B, Greese JT, Newman LE, Cole JR. Pulmonary edema and hydrothorax in swine produced by fumonisin B1 a metabolite of Fusarium. J Vet Diagn Invest 1990; 2:217–21.

    PubMed  CAS  Google Scholar 

  9. Gelderblom WCA, Cawood ME, Snyman SD, Marasas WFO. Fumonisin B1 dosimetry in relation to cancer initiation in rat livers. Carcinogenesis 1994; 15:209–14.

    Article  PubMed  CAS  Google Scholar 

  10. Chu FS, Li GY. Simultaneous, occurrence of Fumonisin B1 and other mycotoxins in moldy corn collected from the People’s Republic of China in regions with high incidence of esophageal cancer. Appl Environ Microbiol 1994; 60:847–52.

    PubMed  CAS  Google Scholar 

  11. Doko MB, Visconti A. Occurrence of Fumonisins B1 and B2 in corn and corn-based human food stuffs in Italy. Food Addit Contam 1994; 11:433–9.

    PubMed  CAS  Google Scholar 

  12. Sydenham EW, Shephard GS, Thiel PG, Marasas WFO, Stockenstrom S. Fumonisin contamination of commercial corn-based human foodstuffs. J Agric Food Chem 1991; 39:2014–8.

    Article  CAS  Google Scholar 

  13. Missmer SA, Suarez L, Felkner M, Wang E, Merrill AH Jr, Rothman KJ, Hendricks KA. Exposure to fumonisin and the occurrence of Neural tube defects along the Texas-Mexico border. Environ Health Perspect 2006; 114:237–41.

    Article  PubMed  Google Scholar 

  14. Qureshi MA, Hagler WM. Effect of Fumonisin B1 exposure on chicken macrophage functions in in vitro. Poultry Sci 1992; 71:104–12.

    CAS  Google Scholar 

  15. Marasas WFO. History, world-wide occurrence and impact. In: Jackson LS, De Vries JW, Bullerman LB, editors. Fumonisins in foods. New York: Plenum Press; 1996. p. 1–17.

    Google Scholar 

  16. Dombrink-Kurtzman MA, Benett GA, Richard JL. An optimized MTT bioassay for determination of cytotoxicity of fumonisins in Turkey lymphocytes. J AOAC Int 1994; 77:512–6.

    PubMed  CAS  Google Scholar 

  17. Gelderblom WCA, Marasas WFO, Vleggaar R, Thiel PG, Cawood ME. Fumonisins— isolation, chemical characterization and biological effects. Mycopathologia 1992; 117:11–6.

    Article  PubMed  CAS  Google Scholar 

  18. Park DL, Rua SM Jr, Mirocha CJ, Abd-Alla ESAM, Weng CY. Mutagenic potentials of fumonisin contaminated corn following ammonia decontamination procedure. Mycopathologia 1992; 117:105–8.

    Article  PubMed  CAS  Google Scholar 

  19. Norred WP, Plattner RD, Vesonder RF, Bacon CW, Voss KA. Effects of secondary metabolites of Fusarium moniliforme on unscheduled synthesis of DNA by rat primary hepatocytes. Food Chem Toxicol 1992; 30:233–7.

    Article  PubMed  CAS  Google Scholar 

  20. Meivar-Levy IM, Sabanay H, Bershadsky AD, Futerman AH. The role of sphingolipids in the maintenance of fibroblast, morphology: the inhibition of protrusional activity, cell spreading, and cytokinesis induced by fumonisin B1 can be reversed by ganglioside GM3. J Biol Chem 1997; 272:1558–64.

    Article  PubMed  CAS  Google Scholar 

  21. International Agency for Research on Cancer (IARC). Summaries and evaluation. Fumonisin B1 2002; 82:301.

    Google Scholar 

  22. Joint FAO/WHO Expert Committee on Food Additives (JECFA). Monographs and evaluations, Fumonisins. (2001); 47. http://www.inchem.org/documents/jecfa/jec mono /v 47je03.htm

  23. Wang E, Norred WP, Bacon C, Riley RT, Merrill AH Jr. Inhibition of sphingolipid biosynthesis by fumonisins: implication for diseases associated with Fusarium moniliforme. J Biol Chem 1991; 266:14486–90.

    PubMed  CAS  Google Scholar 

  24. Yin JJ, Smith MJ, Eppley RM, Page SW, Sphon JA. Effects of fumonisin B1 on lipid peroxidation in membranes. Biochim Biophys Acta 1998; 1371:134–42.

    Article  PubMed  CAS  Google Scholar 

  25. Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nago M. Inhibition of protein serine/threonine phosphatases by Fumonisin B1 a mycotoxin. Biochem Biophys Res Commun. 1996; 220: 160–5.

    Article  PubMed  CAS  Google Scholar 

  26. Sauviat MP, Laurent D, Kohler F, Pellegrin F. Fumonisin, a toxin from the fungus Fusarium moniliforme Sheld, blocks both the calcium current and mechanical activity in frog atrial muscle. Toxicon 1991; 29:1025–31.

    Article  PubMed  CAS  Google Scholar 

  27. Sashidhar RB, Karuna R. Mechanistic implications of fumonisin mycotoxin. In: Subramanyam C, Singh SS, editors. Proceedings of International Meeting on Molecular Mechanisms of Toxicity, Osmania University, Hyderabad, India; 1997. p. 64–9.

  28. Merrill AH Jr, Sullards MC, Wang E, Voss KA, Riley RT. Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins. Environ Health Perspect. 2001; 109:283–9.

    Article  PubMed  CAS  Google Scholar 

  29. Huang C, Dickman M, Henderson G, Jones C. Repression of protein kinase C and stimulation of cAMP response elements by fumonisins a fungal encoded toxin which is a carcinogen. Cancer Res 1995; 55:1655–9.

    PubMed  CAS  Google Scholar 

  30. World Health Organization (WHO). Selected mycotoxins, ochratoxin, trichothecene, ergot. International Programme on Chemical Safety (IPCS), Geneva. Environ Health Criteria 1990; 105:110–56.

  31. Abbas HK, Duke SO, Tanaka T. Phytotoxicity of fumonisins and related compounds. J Toxicol Toxin Rev 1993; 12:225–1.

    Google Scholar 

  32. Abbas HK, Tanaka T, Duke SO, Porter JK, Wray EM, Hodges L, Sessions AE, Wang E, Merrill AH Jr, Riley RT. Fumonisins-AAL-toxin induced disruption of sphingolipid metabolism with accumulation of free sphingoid bases. Plant Physiol 1994; 106:1085–93.

    PubMed  CAS  Google Scholar 

  33. Lynch DV, Dunn TM. An introduction to plant sphingolipids and a review of recent advances in understanding their metabolism and function. New Phytol 2004; 161: 677–702.

    Article  CAS  Google Scholar 

  34. Van Asch MAJ, Rijkenberg FHJ, Coutinho TA. Phytotoxicity of Fumonisin B1, moniliformin and T-2 toxin to corn callus cultures. Phytopathology 1992; 82:1330–2.

    Article  Google Scholar 

  35. Williams LD, Glenn AE, Bacon CW, Smith MA, Riley RT. Evidence for increased sphingoid base-1-phophate lyase activity in corn seedlings after prolonged exposure to FB1. Toxicol Sci 2006; 90:408.

    Google Scholar 

  36. Williams L, Glenn A, Zimeri A, Bacon C, Smith M, Riley R. Fumonisin disruption of ceramide biosynthesis in maize roots and plant development and Fusarium verticilloides induced seedling disease. J Agric Food Chem 2007; 55: 2937–46.

    Article  PubMed  CAS  Google Scholar 

  37. Lowry OH, Rose Brough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:263–75.

    Google Scholar 

  38. Stewart WT, Hawcraft DM. A manual of radiobiology. London: Sidgwick and Jackson; 1981. p. 116–119.

    Google Scholar 

  39. Betina V. (editor). Mycotoxins-production, isolation separation and purification. Amsterdam, Netherlands: Elsevier; 1984. p. 3–36.

  40. Norred WP, Bacon CW, Porter JK, Voss KA. Inhibition of protein synthesis in rat primary hepatocytes. Food Chem Toxicol 1990; 28:233–7.

    Google Scholar 

  41. Norred WP, Bacon CW, Plattner RD, Vesonder RF. Differential cytotoxicity and mycotoxin content among isolates of Fusarium moniliforme. Mycopathologia 1991; 115:37–43.

    Article  PubMed  CAS  Google Scholar 

  42. Norred WP, Wang E, Yoo H, Riley RT, Merill AH Jr. In vitro toxicology of fumonisins and the mechanistic implications. Mycopathologia 1992; 117:73–8.

    Article  PubMed  CAS  Google Scholar 

  43. Gelderblom WCA, Smuts CM, Abel S, Snyman SD, Cawood ME, Van Der Westhuizen L, Swanevelder S. Effect of Fumonisin B1 on protein and lipid synthesis in primary rat hepatocytes. Food Chem Toxicol 1996; 34:361–9.

    Article  PubMed  CAS  Google Scholar 

  44. Shephard GS, Thiel PG, Sydenham EW. Initial studies on the toxicokinetics of fumonisin B1 in rats. Food Chem Toxicol 1992; 30:277–9.

    Article  PubMed  CAS  Google Scholar 

  45. Voss KA, Riley RT, Norred WP, Bacon CW, Meridth FI, Howard PC, Plattner RD, Collins TFX, Hansen DK, Porter JK. An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme. Environ Health Perspect 2001; 109:259–66.

    Article  PubMed  CAS  Google Scholar 

  46. Voss KA, Norred WP, Bacon CW. Subchronic toxi- cological investigations of Fusarium moniliforme—contaminated corn, culture material, and ammoniated culture material. Mycopathologia 1992; 117:97–104.

    Article  PubMed  CAS  Google Scholar 

  47. Sharma RP, Duggyala RR, Voss KA. Demonstration of in situ apoptosis in mouse liver and kidney after short term repeated exposure to Fumonisin B1. J Comp Pathol 1997; 117:371–81.

    Article  PubMed  CAS  Google Scholar 

  48. Thompson WL, Wannemacher RW Jr. In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues. Toxicol Appl Pharmacol 1990; 105:483–91.

    Article  PubMed  CAS  Google Scholar 

  49. Tolleson WH, Dooley KL, Sheldon WG, Thurman JD, Bucci TJ, Howard PC. The mycotoxin fumonisin induces apoptosis in cultured human and in livers and kidneys of rats. In: Jackson LS, De Vries JW, Bullerman LB, editors. Fumonisins in foods. New York: Plenum Press; 1996. p.␣237–250.

  50. Zhang Y, Dickman MB, Jones C. The mycotoxin fumonisin B1 transcriptionally activates p21 promoter through a cis-acting element containing two Sp1 binding sites. J Biol Chem 1999; 274:12367–71.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are thankful to Mr. Amir-ul-Islam of Jonaki, Department of Atomic Energy, Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India, for providing facility for carrying out the in vitro translation studies.

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Correspondence to R. B. Sashidhar.

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Karuna, R., Sashidhar, R.B. The mycotoxin fumonisin B1 inhibits eukaryotic protein synthesis: in vitro and in vivo studies. Mycopathologia 165, 37–49 (2008). https://doi.org/10.1007/s11046-007-9075-y

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