Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network
Deoxynivalenol (DON), produced by the plant pathogens Fusarium graminearum and Fusarium culmorum, is one of the most common mycotoxins, contaminating cereal and cereal-derived products. Although worldwide contamination of food and feed poses health threats to humans and animals, pigs are particularl...
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| Format: | Article |
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MDPI AG
2016-09-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/9/264 |
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| author | Alexandra Springler Sabine Hessenberger Gerd Schatzmayr Elisabeth Mayer |
| author_facet | Alexandra Springler Sabine Hessenberger Gerd Schatzmayr Elisabeth Mayer |
| author_sort | Alexandra Springler |
| collection | DOAJ |
| description | Deoxynivalenol (DON), produced by the plant pathogens Fusarium graminearum and Fusarium culmorum, is one of the most common mycotoxins, contaminating cereal and cereal-derived products. Although worldwide contamination of food and feed poses health threats to humans and animals, pigs are particularly susceptible to this mycotoxin. DON derivatives, such as deepoxy-deoxynivalenol (DOM-1), are produced by bacterial transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Intestinal epithelial cells are the initial barrier against these food- and feed-borne toxins. The present study confirms DON-induced activation of MAPK p44/42 and inhibition of p44/42 by MAPK-inhibitor U0126 monoethanolate. Influence of DON and DOM-1 on transepithelial electrical resistance (TEER), viability and expression of seven tight junction proteins (TJ), as well as the potential of U0126 to counteract DON-induced effects, was assessed. While DOM-1 showed no effect, DON significantly reduced TEER of differentiated IPEC-J2 and decreased expression of claudin-1 and -3, while leaving claudin-4; ZO-1, -2, and -3 and occludin unaffected. Inhibition of p44/42 counteracted DON-induced TEER decrease and restored claudin-3, but not claudin-1 expression. Therefore, effects of DON on TEER and claudin-3 are at least partially p44/42 mediated, while effects on viability and claudin-1 are likely mediated via alternative pathways. |
| first_indexed | 2024-04-11T13:00:35Z |
| format | Article |
| id | doaj.art-8b30a26c367842b9a2fa84458aa6134a |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T13:00:35Z |
| publishDate | 2016-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-8b30a26c367842b9a2fa84458aa6134a2022-12-22T04:22:58ZengMDPI AGToxins2072-66512016-09-018926410.3390/toxins8090264toxins8090264Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction NetworkAlexandra Springler0Sabine Hessenberger1Gerd Schatzmayr2Elisabeth Mayer3Biomin Research Center, Technopark 1, 3430 Tulln an der Donau, AustriaBiomin Research Center, Technopark 1, 3430 Tulln an der Donau, AustriaBiomin Research Center, Technopark 1, 3430 Tulln an der Donau, AustriaBiomin Research Center, Technopark 1, 3430 Tulln an der Donau, AustriaDeoxynivalenol (DON), produced by the plant pathogens Fusarium graminearum and Fusarium culmorum, is one of the most common mycotoxins, contaminating cereal and cereal-derived products. Although worldwide contamination of food and feed poses health threats to humans and animals, pigs are particularly susceptible to this mycotoxin. DON derivatives, such as deepoxy-deoxynivalenol (DOM-1), are produced by bacterial transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Intestinal epithelial cells are the initial barrier against these food- and feed-borne toxins. The present study confirms DON-induced activation of MAPK p44/42 and inhibition of p44/42 by MAPK-inhibitor U0126 monoethanolate. Influence of DON and DOM-1 on transepithelial electrical resistance (TEER), viability and expression of seven tight junction proteins (TJ), as well as the potential of U0126 to counteract DON-induced effects, was assessed. While DOM-1 showed no effect, DON significantly reduced TEER of differentiated IPEC-J2 and decreased expression of claudin-1 and -3, while leaving claudin-4; ZO-1, -2, and -3 and occludin unaffected. Inhibition of p44/42 counteracted DON-induced TEER decrease and restored claudin-3, but not claudin-1 expression. Therefore, effects of DON on TEER and claudin-3 are at least partially p44/42 mediated, while effects on viability and claudin-1 are likely mediated via alternative pathways.http://www.mdpi.com/2072-6651/8/9/264transepithelial electrical resistancemycotoxinIPEC-J2tight junctionsdeoxynivalenolde-epoxy deoxynivalenol |
| spellingShingle | Alexandra Springler Sabine Hessenberger Gerd Schatzmayr Elisabeth Mayer Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network Toxins transepithelial electrical resistance mycotoxin IPEC-J2 tight junctions deoxynivalenol de-epoxy deoxynivalenol |
| title | Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network |
| title_full | Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network |
| title_fullStr | Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network |
| title_full_unstemmed | Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network |
| title_short | Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network |
| title_sort | early activation of mapk p44 42 is partially involved in don induced disruption of the intestinal barrier function and tight junction network |
| topic | transepithelial electrical resistance mycotoxin IPEC-J2 tight junctions deoxynivalenol de-epoxy deoxynivalenol |
| url | http://www.mdpi.com/2072-6651/8/9/264 |
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