Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-27T05:34:29.714Z Has data issue: false hasContentIssue false
  • English
  • Français

Fusarium mycotoxin-contaminated wheat containing deoxynivalenol alters the gene expression in the liver and the jejunum of broilers

Published online by Cambridge University Press:  19 September 2011

B. Dietrich ,
S. Neuenschwander ,
B. Bucher  and
C. Wenk
B. Dietrich*
Affiliation:
Nutrition Biology, Institute of Agricultural Sciences, Swiss Federal Institute of Technology (ETHZ), Universitätsstrasse 2, CH-8092 Zurich, Switzerland
S. Neuenschwander
Affiliation:
Breeding Biology, Institute of Agricultural Sciences, Swiss Federal Institute of Technology (ETHZ), Tannenstrasse 1, CH-8092 Zurich, Switzerland
B. Bucher
Affiliation:
Nutrition Biology, Institute of Agricultural Sciences, Swiss Federal Institute of Technology (ETHZ), Universitätsstrasse 2, CH-8092 Zurich, Switzerland
C. Wenk
Affiliation:
Nutrition Biology, Institute of Agricultural Sciences, Swiss Federal Institute of Technology (ETHZ), Universitätsstrasse 2, CH-8092 Zurich, Switzerland
Get access

Abstract

The effects of mycotoxins in the production of animal feed were investigated using broiler chickens. For the feeding trial, naturally Fusarium mycotoxin-contaminated wheat was used, which mainly contained deoxynivalenol (DON). The main effects of DON are reduction of the feed intake and reduced weight gain of broilers. At the molecular level, DON binds to the 60 S ribosomal subunit and subsequently inhibits protein synthesis at the translational level. However, little is known about other effects of DON, for example, at the transcriptional level. Therefore, a microarray analysis was performed, which allows the investigation of thousands of transcripts in one experiment. In the experiment, 20 broilers were separated into four groups of five broilers each at day 1 after hatching. The diets consisted of a control diet and three diets with calculated, moderate concentrations of 1.0, 2.5 and 5.0 mg DON/kg feed, which was attained by exchanging uncontaminated wheat with naturally mycotoxin-contaminated wheat up to the intended DON concentration. The broilers were held at standard conditions for 23 days. Three microarrays were used per group to determine the significant alterations of the gene expression in the liver (P < 0.05), and qPCR was performed on the liver and the jejunum to verify the results. No significant difference in BW, feed intake or feed conversion rate was observed. The nutrient uptake into the hepatic and jejunal cells seemed to be influenced by genes: SLC2A5 (fc: −1.54, DON2.5), which facilitates glucose and fructose transport and SLC7A10 (fc: +1.49, DON5), a transporter of d-serine and other neutral amino acids. In the jejunum, the palmitate transport might be altered by SLC27A4 (fc: −1.87, DON5) and monocarboxylates uptake by SLC16A1 (fc: −1.47, DON5). The alterations of the SLC gene expression may explain the reduced weight gain of broilers chronically exposed to DON-contaminated wheat. The decreased expressions of EIF2AK3 (fc: −1.29, DON2.5/5) and DNAJC3 (fc: −1.44, DON2.5) seem to be related to the translation inhibition. The binding of DON to the 60 S ribosomal subunit and the subsequent translation inhibition might be counterbalanced by the downregulation of EIF2AK3 and DNAJC3. The genes PARP1, MPG, EME1, XPAC, RIF1 and CHAF1B are mainly related to single-strand DNA modifications and showed an increased expression in the group with 5 mg DON/kg feed. The results indicate that significantly altered gene expression was already occurring at 2.5 mg DON/kg feed.

Keywords

deoxynivalenolliverbroilergene expressionmicroarray
Type
Full Paper
Information
animal , Volume 6 , Issue 2 , 03 January 2012 , pp. 278 - 291
Copyright
Copyright © The Animal Consortium 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abraham, J, Lemmers, B, Hande, MP, Moynahan, ME, Chahwan, C, Ciccia, A, Essers, J, Hanada, K, Chahwan, R, Khaw, AK, McPherson, P, Shehabeldin, A, Laister, R, Arrowsmith, C, Kanaar, R, West, SC, Jasin, M, Hakem, R 2003. Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells. EMBO Journal 22, 6137–6147.CrossRefGoogle ScholarPubMed
Aeschbacher, K, Messikommer, R, Meile, L, Wenk, C 2005. Bt176 corn in poultry nutrition: physiological characteristics and fate of recombinant plant DNA in chickens. Poultry Science 84, 385–394.CrossRefGoogle ScholarPubMed
Awad, WA, Bohm, J, Razzazi-Fazeli, E, Hulan, HW, Zentek, J 2004. Effects of deoxynivalenol on general performance and electrophysiological properties of intestinal mucosa of broiler chickens. Poultry Science 83, 1964–1972.CrossRefGoogle ScholarPubMed
Awad, WA, Ghareeb, K, Bohm, J, Razzazi, E, Hellweg, P, Zentek, J 2008. The impact of the Fusarium toxin deoxynivalenol (DON) on poultry. International Journal of Poultry Science 7, 827–842.CrossRefGoogle Scholar
Azcona-Olivera, JI, Ouyang, Y, Murtha, J, Chu, FS, Pestka, JJ 1995. Induction of cytokine mRNAs in mice after oral exposure to the trichothecene vomitoxin (deoxynivalenol): relationship to toxin distribution and protein synthesis inhibition. Toxicology and Applied Pharmacology 133, 109–120.CrossRefGoogle Scholar
Bondy, GS, Pestka, JJ 2000. Immunomodulation by fungal toxins. Journal of Toxicology and Environmental Health, Part B: Critical Reviews 3, 109–143.Google ScholarPubMed
Bosserhoff, AK, Moser, M, Scholmerich, J, Buettner, R, Hellerbrand, C 2003. Specific expression and regulation of the new melanoma inhibitory activity-related gene MIA2 in hepatocytes. Journal of Biological Chemistry 278, 15225–15231.CrossRefGoogle ScholarPubMed
Chen, CY, Gherzi, R, Ong, SE, Chan, EL, Raijmakers, R, Pruijn, GJ, Stoecklin, G, Moroni, C, Mann, M, Karin, M 2001. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107, 451–464.CrossRefGoogle ScholarPubMed
De Walle, JV, Sergent, T, Piront, N, Toussaint, O, Schneider, YJ, Larondelle, Y 2010. Deoxynivalenol affects in vitro intestinal epithelial cell barrier integrity through inhibition of protein synthesis. Toxicology and Applied Pharmacology 245, 291–298.CrossRefGoogle ScholarPubMed
Diesing, AK, Nossol, C, Panther, P, Walk, N, Post, A, Kluess, J, Kreutzmann, P, Danicke, S, Rothkotter, HJ, Kahlert, S 2011. Mycotoxin deoxynivalenol (DON) mediates biphasic cellular response in intestinal porcine epithelial cell lines IPEC-1 and IPEC-J2. Toxicology Letters 200, 8–18.CrossRefGoogle ScholarPubMed
EFSA 2004. Opinion of the Scientific Panel on Contaminants in the Food Chain on a request from the Commission related to Deoxynivalenol as undesirable substance in animal feed. The EFSA Journal 89, 1–35.Google Scholar
European Union 2006. 2006/576/EC: Commission Recommendation of 17 August 2006 on the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fumonisins in products intended for animal feeding. Official Journal – European Union Legislation 49, 7–9.Google Scholar
Frankic, T, Pajk, T, Rezar, V, Levart, A, Salobir, J 2006. The role of dietary nucleotides in reduction of DNA damage induced by T-2 toxin and deoxynivalenol in chicken leukocytes. Food and Chemical Toxicology 44, 1838–1844.CrossRefGoogle ScholarPubMed
Gale, M Jr, Blakely, CM, Hopkins, DA, Melville, MW, Wambach, M, Romano, PR, Katze, MG 1998. Regulation of interferon-induced protein kinase PKR: modulation of P58IPK inhibitory function by a novel protein, P52rIPK. Molecular and Cellular Biology 18, 859–871.CrossRefGoogle ScholarPubMed
Harhaj, NS, Antonetti, DA 2004. Regulation of tight junctions and loss of barrier function in pathophysiology. International Journal of Biochemistry & Cell Biology 36, 1206–1237.CrossRefGoogle ScholarPubMed
Jin, Y, Penning, TM 2007. Aldo-keto reductases and bioactivation/detoxication. Annual Review of Pharmacology and Toxicology 47, 263–292.CrossRefGoogle ScholarPubMed
Kanai, Y, Segawa, H, Miyamoto, K, Uchino, H, Takeda, E, Endou, H 1998. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). Journal of Biological Chemistry 273, 23629–23632.CrossRefGoogle ScholarPubMed
Kawata, K, Yokoo, H, Shimazaki, R, Okabe, S 2007. Classification of heavy-metal toxicity by human DNA microarray analysis. Environmental Science and Technology 41, 3769–3774.CrossRefGoogle ScholarPubMed
Lambert, DW, Wood, IS, Ellis, A, Shirazi-Beechey, SP 2002. Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. British Journal of Cancer 86, 1262–1269.CrossRefGoogle ScholarPubMed
Liu, X, Xiong, F, Wei, X, Yang, H, Zhou, R 2009. LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells. Cancer 100, 2335–2340.Google ScholarPubMed
Lun, AK, Moran, ET Jr, Young, LG, McMillan, EG 1989. Absorption and elimination of an oral dose of 3H-deoxynivalenol in colostomized and intact chickens. Bulletin of Environmental Contamination and Toxicology 42, 919–925.CrossRefGoogle ScholarPubMed
Maresca, M, Mahfoud, R, Garmy, N, Fantini, J 2002. The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells. Journal of Nutrition 132, 2723–2731.CrossRefGoogle ScholarPubMed
Marzocco, S, Russo, R, Bianco, G, Autore, G, Severino, L 2009. Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages. Toxicology Letters 189, 21–26.CrossRefGoogle ScholarPubMed
Mello, JA, Sillje, HH, Roche, DM, Kirschner, DB, Nigg, EA, Almouzni, G 2002. Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway. EMBO Reports 3, 329–334.CrossRefGoogle Scholar
Miller, KA, Yoshikawa, DM, McConnell, IR, Clark, R, Schild, D, Albala, JS 2002. RAD51C interacts with RAD51B and is central to a larger protein complex in vivo exclusive of RAD51. Journal of Biological Chemistry 277, 8406–8411.CrossRefGoogle ScholarPubMed
Mukherjee, D, Gao, M, O'Connor, JP, Raijmakers, R, Pruijn, G, Lutz, CS, Wilusz, J 2002. The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements. EMBO Journal 21, 165–174.CrossRefGoogle ScholarPubMed
Nakauchi, J, Matsuo, H, Kim, DK, Goto, A, Chairoungdua, A, Cha, SH, Inatomi, J, Shiokawa, Y, Yamaguchi, K, Saito, I, Endou, H, Kanai, Y 2000. Cloning and characterization of a human brain Na(+)-independent transporter for small neutral amino acids that transports D-serine with high affinity. Neuroscience Letters 287, 231–235.CrossRefGoogle ScholarPubMed
National Research Council 1994. Nutrient requirements of poultry. National Academy Press, Washington, DC.Google Scholar
O'Brien, PJ, Ellenberger, T 2004. Dissecting the broad substrate specificity of human 3-methyladenine-DNA glycosylase. Journal of Biological Chemistry 279, 9750–9757.CrossRefGoogle ScholarPubMed
Paschoud, S, Dogar, AM, Kuntz, C, Grisoni-Neupert, B, Richman, L, Kuhn, LC 2006. Destabilization of interleukin-6 mRNA requires a putative RNA stem-loop structure, an AU-rich element, and the RNA-binding protein AUF1. Molecular and Cellular Biology 26, 8228–8241.CrossRefGoogle ScholarPubMed
Pepper, SD, Saunders, EK, Edwards, LE, Wilson, CL, Miller, CJ 2007. The utility of MAS5 expression summary and detection call algorithms. BMC Bioinformatics 8, 273.CrossRefGoogle ScholarPubMed
Pestka, JJ 2007. Deoxynivalenol: toxicity, mechanisms and animal health risks. Animal Feed Science and Technology 137, 283–298.CrossRefGoogle Scholar
Pestka, JJ 2008. Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Additives and Contaminants, 1–13.Google ScholarPubMed
Pestka, JJ 2010. Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Archives of Toxicology 84, 663–679.CrossRefGoogle ScholarPubMed
Pinton, P, Nougayrede, JP, Del Rio, JC, Moreno, C, Marin, DE, Ferrier, L, Bracarense, AP, Kolf-Clauw, M, Oswald, IP 2009. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression. Toxicology and Applied Pharmacology 237, 41–48.CrossRefGoogle ScholarPubMed
Plummer, ER, Calvert, H 2007. Targeting poly(ADP-ribose) polymerase: a two-armed strategy for cancer therapy. Clinical Cancer Research 13, 6252–6256.CrossRefGoogle ScholarPubMed
Prelusky, DB, Gerdes, RG, Underhill, KL, Rotter, BA, Jui, PY, Trenholm, HL 1994. Effects of low-level dietary deoxynivalenol on haematological and clinical parameters of the pig. Natural Toxins 2, 97–104.CrossRefGoogle ScholarPubMed
Rajasingh, J, Bord, E, Luedemann, C, Asai, J, Hamada, H, Thorne, T, Qin, G, Goukassian, D, Zhu, Y, Losordo, DW, Kishore, R 2006. IL-10-induced TNF-alpha mRNA destabilization is mediated via IL-10 suppression of p38 MAP kinase activation and inhibition of HuR expression. FASEB Journal 20, 2112–2114.CrossRefGoogle ScholarPubMed
Robbana-Barnat, S, Loridon-Rosa, B, Cohen, H, Lafarge-Frayssinet, C, Neish, GA, Frayssinet, C 1987. Protein synthesis inhibition and cardiac lesions associated with deoxynivalenol ingestion in mice. Food Additives and Contaminants 4, 49–56.CrossRefGoogle ScholarPubMed
Ron, D 2002. Translational control in the endoplasmic reticulum stress response. Journal of Clinical Investigation 110, 1383–1388.CrossRefGoogle ScholarPubMed
Rotter, BA, Prelusky, DB, Pestka, JJ 1996. Toxicology of deoxynivalenol (vomitoxin). Journal of Toxicology and Environmental Health 48, 1–34.CrossRefGoogle ScholarPubMed
Schilders, G, van Dijk, E, Raijmakers, R, Pruijn, GJ 2006. Cell and molecular biology of the exosome: how to make or break an RNA. International Review of Cytology 251, 159–208.CrossRefGoogle ScholarPubMed
Scott, TA, Hall, JW 1998. Using acid insoluble ash marker ratios (diet : digesta) to predict digestibility of wheat and barley metabolizable energy and nitrogen retention in broiler chicks. Poultry Science 77, 674–679.CrossRefGoogle ScholarPubMed
Sergent, T, Parys, M, Garsou, S, Pussemier, L, Schneider, YJ, Larondelle, Y 2006. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. Toxicology Letters 164, 167–176.CrossRefGoogle ScholarPubMed
Shifrin, VI, Anderson, P 1999. Trichothecene mycotoxins trigger a ribotoxic stress response that activates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase and induces apoptosis. Journal of Biological Chemistry 274, 13985–13992.CrossRefGoogle ScholarPubMed
Shimamoto, T, Tanimura, T, Yoneda, Y, Kobayakawa, Y, Sugasawa, K, Hanaoka, F, Oka, M, Okada, Y, Tanaka, K, Kohno, K 1995. Expression and functional analyses of the Dxpa gene, the Drosophila homolog of the human excision repair gene XPA. Journal of Biological Chemistry 270, 22452–22459.CrossRefGoogle ScholarPubMed
Silverman, J, Takai, H, Buonomo, SB, Eisenhaber, F, de Lange, T 2004. Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint. Genes and Development 18, 2108–2119.CrossRefGoogle ScholarPubMed
Stahl, A, Hirsch, DJ, Gimeno, RE, Punreddy, S, Ge, P, Watson, N, Patel, S, Kotler, M, Raimondi, A, Tartaglia, LA, Lodish, HF 1999. Identification of the major intestinal fatty acid transport protein. Molecular Cell 4, 299–308.CrossRefGoogle ScholarPubMed
Swamy, HV, Smith, TK, Karrow, NA, Boermans, HJ 2004. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on growth and immunological parameters of broiler chickens. Poultry Science 83, 533–543.CrossRefGoogle ScholarPubMed
Swamy, HV, Smith, TK, Cotter, PF, Boermans, HJ, Sefton, AE 2002. Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on production and metabolism in broilers. Poultry Science 81, 966–975.CrossRefGoogle ScholarPubMed
Takezako, N, Hayakawa, M, Hayakawa, H, Aoki, S, Yanagisawa, K, Endo, H, Tominaga, S 2006. ST2 suppresses IL-6 production via the inhibition of IkappaB degradation induced by the LPS signal in THP-1 cells. Biochemical and Biophysical Research Communications 341, 425–432.CrossRefGoogle ScholarPubMed
Ueno, Y 1984. Toxicological features of T-2 toxin and related trichothecenes. Fundamental and Applied Toxicology 4, S124–S132.CrossRefGoogle ScholarPubMed
van Dijk, EL, Schilders, G, Pruijn, GJ 2007. Human cell growth requires a functional cytoplasmic exosome, which is involved in various mRNA decay pathways. RNA 13, 1027–1035.CrossRefGoogle ScholarPubMed
van Huizen, R, Martindale, JL, Gorospe, M, Holbrook, NJ 2003. P58IPK, a novel endoplasmic reticulum stress-inducible protein and potential negative regulator of eIF2alpha signaling. Journal of Biological Chemistry 278, 15558–15564.CrossRefGoogle ScholarPubMed
Wong, S, Schwartz, RC, Pestka, JJ 2001. Superinduction of TNF-alpha and IL-6 in macrophages by vomitoxin (deoxynivalenol) modulated by mRNA stabilization. Toxicology 161, 139–149.CrossRefGoogle ScholarPubMed
Xu, CS, Chang, CF, Yuan, JY, Li, WQ, Han, HP, Yang, KJ, Zhao, LF, Li, YC, Zhang, HY, Rahman, S, Zhang, JB 2005. Expressed genes in regenerating rat liver after partial hepatectomy. World Journal of Gastroenterology 11, 2932–2940.CrossRefGoogle ScholarPubMed
Yang, GH, Li, S, Pestka, JJ 2000. Down-regulation of the endoplasmic reticulum chaperone GRP78/BiP by vomitoxin (Deoxynivalenol). Toxicology and Applied Pharmacology 162, 207–217.CrossRefGoogle ScholarPubMed
Yoshizawa, T, Cote, LM, Swanson, SP, and Buck, WB 1986. Confirmation of DOM-1, a de-epoxidation metabolite of deoxynivalenol, in biological fluids of lactating cows. Agricultural and Biological Chemistry 50, 227–229.Google Scholar