Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations

Sergent, Thérèse; Parys, Marie; Garsou, Serge; Pussemier, Luc; Schneider, Yves‐Jacques; Larondelle, Yvan

doi:10.1016/j.toxlet.2005.12.006

Cited by 171 publications

(107 citation statements)

References 39 publications

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“…*P , 0.05; **P , 0.01; ***P , 0.001. (Sergent et al, 2006). Among the proteins mentioned was TJP1 (fc: 21.52, DON5), which was downregulated in our experiment in the liver, which was also measured with qPCR (fc: 21.66).…”

Section: Translation Initiationmentioning

confidence: 53%

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

Dietrich

Neuenschwander

Bucher

et al. 2012

Animal

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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: 21.54, DON2.5), which facilitates glucose and fructose transport and SLC7A10 (fc: 11.49, DON5), a transporter of D-serine and other neutral amino acids. In the jejunum, the palmitate transport might be altered by SLC27A4 (fc: 21.87, DON5) and monocarboxylates uptake by SLC16A1 (fc: 21.47, 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: 21.29, DON2.5/5) and DNAJC3 (fc: 21.44, 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.

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Section: Translation Initiationmentioning

confidence: 53%

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

Dietrich

Neuenschwander

Bucher

et al. 2012

Animal

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“…According to these reports, DON (a chemical ribosomal stress agent) induced SOCS proteins after the onset of proinflammatory cytokine decline, and this induction was involved in impaired growth hormone signaling in liver. Moreover, increasing evidence indicates mucosal ribosomal stress disrupts epithelial integrity (38,39,59), particularly regulating cellular growth and survival (71,72). Furthermore, some ribosomal insults can induce G 2 /M cell cycle arrest via p21 expression in human epithelium (73).…”

Section: Discussionmentioning

confidence: 99%

“…Several epidemiological studies suggested links between ribosomal stress and human mucosal epithelial illness, including intestinal inflammatory diseases (33)(34)(35). Mechanistically, chemical ribosomal stress alters intestinal mucosal integrity by interfering with transepithelial resistance, epithelial differentiation, and nutrient absorption, the last of which is associated with anorexia and weight loss (36)(37)(38)(39). Moreover, ribosomal stress triggers mucosal and systemic inflammation, mostly due to the enhanced production of proinflammatory mediators in immune-related cells (40)(41)(42)(43).…”

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confidence: 99%

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Hun

Choi

Kim

et al. 2013

The Journal of Immunology

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Although the activation of B cells in the gastrointestinal tract is of great importance in the context of immunity to pathogens and mucosal inflammatory diseases, little is known about the mechanisms responsible for the local activation of B cells in the subepithelial area of the intestine. Epithelium-derived BAFF is the major modulator of B cell development and Ig class switching. The present study was performed to address the molecular mechanism of BAFF expression in gut epithelial cells in the presence of proinflammatory stimuli. Inflammation-induced BAFF expression in mucosal epithelial cells might be responsible for diverse mucosa-associated diseases linked to intestinal inflammation and autoimmunity. Although BAFF was marginally expressed in unstimulated epithelial cells, BAFF mRNA was significantly upregulated by proinflammatory IFN-γ. Furthermore, IFN-γ triggered JAK/STAT1 signals via the cytokine receptor, which contributed to epithelial BAFF upregulation. In terms of signaling intervention, ribosomal insult attenuated IFN-γ–activated JAK/STAT signal transduction and subsequent BAFF induction in gut epithelial cells. Ribosomal insults led to the superinduction of SOCS3 by enhancing its mRNA stability via HuR RNA-binding protein. Upregulated SOCS3 then contributed to the blocking of the JAK/STAT-linked signal, which mediated BAFF suppression by ribosomal stress. All of these findings show that ribosomal stress–induced SOCS3 plays a novel regulatory role in epithelial BAFF production, suggesting that epithelial ribosomal dysfunction in association with SOCS3 may be a promising therapeutic point in BAFF-associated human mucosal diseases.

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“…It should also be noted that DON can enhance the permeability of enterocyte membranes (Sergent et al 2006, Pinton et al 2009). DON intoxification also suppresses cytotoxicity and protein synthesis, and increases the permeability of the gut wall (Kouadio et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Zearalenone and deoxynivalenol mycotoxicosis in dairy cattle herds

Marczuk

Obremski

Lutnicki

et al. 2012

Polish Journal of Veterinary Sciences

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Mycotoxin contaminations pose a growing problem in animal production from the economic and toxicological point of view. Clinical symptoms of mycotoxicosis are relatively unspecific, making the disease difficult to diagnose. This study presents a clinical case of dairy cattle infected with natural mycotoxins produced by fungi of the genus Fusarium (zearalenone [ZEA] and deoxynivalenol [DON]) in eastern Poland. In dead and infected cows, the presence of ZEA and DON was determined in the blood serum, significant changes were observed in blood morphological and biochemical profiles, extravasations and bowel inflammations were also observed. The results reported testify to an acute autoimmune process in the intestines as well as immunosuppression.

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Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations

Cited by 171 publications

References 39 publications

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

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

SOCS3 Regulates BAFF in Human Enterocytes under Ribosomal Stress

Zearalenone and deoxynivalenol mycotoxicosis in dairy cattle herds

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