Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells
Abstract
:1. Introduction
2. Results
2.1. Deoxynivalenol (DON) Impaired the Barrier Function of Intestinal Porcine Epithelial Cells (IPEC-J2)
2.2. DON Decreased the Expression of Tight Junction Proteins
2.3. The Role of Apoptosis in DON Toxicity
2.4. The Effect of DON on Glucose Consumption
2.5. Identification of Phosphopeptide and Phosphoprotein
2.6. Properties of Phosphorylated Proteins
2.7. Validation of Selected Proteins
3. Discussion
3.1. DON-Induced Changes—Impact on Apoptosis
3.2. DON-Induced Changes-Impact on Intestinal Barrier
3.3. DON-Induced Changes—Impact on Intestinal Immune Responses
3.4. DON-Induced Changes—Impact on the Absorption of Glucose
4. Conclusions
5. Materials and Methods
5.1. Cell Culture and Reagents
5.2. DON Exposure
5.3. Measurement of Transepithelial Electrical Resistance (TEER)
5.4. Glucose Assay
5.5. Protein Analyses
5.5.1. Sample Preparation
5.5.2. Western Blot Analysis
5.5.3. Protein Digestion, iTRAQ Labeling and Phosphopeptide Enrichment
5.6. Liquid Chromatography-Tandem Mass Spectromety (LC-MS/MS) Analysis
5.7. Data Analysis
5.8. Bioinformatic Analysis of Phosphoproteomic Data
5.9. Statistical Analysis
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Montes, R.; Segarra, R.; Castillo, M.A. Trichothecenes in breakfast cereals from the Spanish retail market. J. Food Compos. Anal. 2012, 27, 38–44. [Google Scholar] [CrossRef]
- Tralamazza, S.M.; Bemvenuti, R.H.; Zorzete, P.; de Souza Garcia, F.; Corrêa, B. Fungal diversity and natural occurrence of deoxynivalenol and zearalenone in freshly harvested wheat grains from Brazil. Food Chem. 2016, 196, 445–450. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Lu, Y.; Wang, L.; Chang, F.; Yang, L. Occurrence of deoxynivalenol in wheat, Hebei province, China. Food Chem. 2016, 197, 1271–1274. [Google Scholar] [CrossRef] [PubMed]
- Warth, B.; Sulyok, M.; Fruhmann, P.; Berthiller, F.; Schuhmacher, R.; Hametner, C.; Adam, G.; Fröhlich, J.; Krska, R. Assessment of human deoxynivalenol exposure using an LC-MS/MS based biomarker method. Toxicol. Lett. 2012, 211, 85–90. [Google Scholar] [CrossRef] [PubMed]
- Zain, M.E. Impact of mycotoxins on humans and animals. J. Saudi Chem. Soc. 2011, 15, 129–144. [Google Scholar] [CrossRef]
- Waskiewicz, A.; Beszterda, M.; Kostecki, M.; Zielonka, L.; Golinski, P.; Gajecki, M. Deoxynivalenol in the gastrointestinal tract of immature gilts under per os toxin application. Toxins 2014, 6, 973–987. [Google Scholar] [CrossRef] [PubMed]
- Lucioli, J.; Pinton, P.; Callu, P.; Laffitte, J.; Grosjean, F.; Kolf-Clauw, M.; Oswald, I.P.; Bracarense, A.P. The food contaminant deoxynivalenol activates the mitogen activated protein kinases in the intestine: Interest of ex vivo models as an alternative to in vivo experiments. Toxicon 2013, 66, 31–36. [Google Scholar] [CrossRef] [PubMed]
- Nossol, C.; Diesing, A.K.; Kahlert, S.; Kersten, S.; Kluess, J.; Ponsuksili, S.; Hartig, R.; Wimmers, K.; Danicke, S.; Rothkotter, H.J. Deoxynivalenol affects the composition of the basement membrane proteins and influences en route the migration of CD16+ cells into the intestinal epithelium. Mycotoxin Res. 2013, 29, 245–254. [Google Scholar] [CrossRef] [PubMed]
- Lessard, M.; Savard, C.; Deschene, K.; Lauzon, K.; Pinilla, V.A.; Gagnon, C.A.; Lapointe, J.; Guay, F.; Chorfi, Y. Impact of deoxynivalenol (DON) contaminated feed on intestinal integrity and immune response in swine. Food Chem. Toxicol. 2015, 80, 7–16. [Google Scholar] [CrossRef] [PubMed]
- Odenwald, M.A.; Turner, J.R. Intestinal permeability defects: Is it time to treat? Clin. Gastroenterol. Hepatol. 2013, 11, 1075–1083. [Google Scholar] [CrossRef] [PubMed]
- Prelusky, D.B.; Hartin, K.E.; Trenholm, H.L.; Miller, J.D. Pharmacokinetic fate of 14C-labeled deoxynivalenol in swine. Fundam. Appl. Toxicol. 1988, 10, 276–286. [Google Scholar] [CrossRef]
- Pinton, P.; Tsybulskyy, D.; Lucioli, J.; Laffitte, J.; Callu, P.; Lyazhri, F.; Grosjean, F.; Bracarense, A.P.; Kolf-Clauw, M.; Oswald, I.P. Toxicity of deoxynivalenol and its acetylated derivatives on the intestine: Differential effects on morphology, barrier function, tight junction proteins, and mitogen-activated protein kinases. Toxicol. Sci. 2012, 130, 180–190. [Google Scholar] [CrossRef] [PubMed]
- Diesing, A.K.; Nossol, C.; Panther, P.; Walk, N.; Post, A.; Kluess, J.; Kreutzmann, P.; Danicke, S.; Rothkotter, H.J.; Kahlert, S. Mycotoxin deoxynivalenol (DON) mediates biphasic cellular response in intestinal porcine epithelial cell lines IPEC-1 and IPEC-J2. Toxicol. Lett. 2011, 200, 8–18. [Google Scholar] [CrossRef] [PubMed]
- Pinton, P.; Graziani, F.; Pujol, A.; Nicoletti, C.; Paris, O.; Ernouf, P.; Pasquale, E.D.; Perrier, J.; Oswald, I.P.; Maresca, M. Deoxynivalenol inhibits the expression by goblet cells of intestinal mucins through a PKR and MAP kinase dependent repression of the resistin-like molecule β. Mol. Nutr. Food Res. 2015, 59, 1076–1087. [Google Scholar] [CrossRef] [PubMed]
- Graziani, F.; Pujol, A.; Nicoletti, C.; Pinton, P.; Armand, L.; Pasquale, E.D.; Oswald, I.P.; Perrier, J.; Maresca, M. The food-associated ribotoxin deoxynivalenol modulates inducible NO synthase in human intestinal cell model. Toxicol. Sci. 2015, 145, 372–382. [Google Scholar] [CrossRef] [PubMed]
- Awad, W.A.; Ghareeb, K.; Zentek, J. Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens. Vet. J. 2014, 202, 188–190. [Google Scholar] [CrossRef] [PubMed]
- Von Stechow, L.; Francavilla, C.; Olsen, J.V. Recent findings and technological advances in phosphoproteomics for cells and tissues. Expert Rev. Proteom. 2015, 12, 469–487. [Google Scholar] [CrossRef] [PubMed]
- Pan, X.; Whitten, D.A.; Wu, M.; Chan, C.; Wilkerson, C.G.; Pestka, J.J. Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage. Toxicol. Appl. Pharm. 2013, 268, 201–211. [Google Scholar] [CrossRef] [PubMed]
- Pan, X.; Whitten, D.A.; Wilkerson, C.G.; Pestka, J.J. Dynamic changes in ribosome-associated proteome and phosphoproteome during deoxynivalenol-induced translation inhibition and ribotoxic stress. Toxicol. Sci. 2014, 138, 217–233. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Nelson, R.W.; Ros, A. Towards analysis of proteins in single cells: A quantitative approach employing iTRAQ labels with MALDI Mass Spectrometry realized with a Microfluidic Platform. Anal. Chem. 2016, 88, 6272–6279. [Google Scholar] [CrossRef] [PubMed]
- Goyarts, T.; Dänicke, S. Bioavailability of the Fusarium toxin deoxynivalenol (DON) from naturally contaminated wheat for the pig. Toxicol. Lett. 2006, 163, 171–182. [Google Scholar] [CrossRef] [PubMed]
- Danicke, S.; Valenta, H.; Doll, S. On the toxicokinetics and the metabolism of deoxynivalenol (DON) in the pig. Arch. Anim. Nutr. 2004, 58, 169–180. [Google Scholar] [CrossRef] [PubMed]
- Schierack, P.; Nordhoff, M.; Pollmann, M.; Weyrauch, K.D.; Amasheh, S.; Lodemann, U.; Jores, J.; Tachu, B.; Kleta, S.; Blikslager, A.; et al. Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine. Histochem. Cell Biol. 2006, 125, 293–305. [Google Scholar] [CrossRef] [PubMed]
- Nossol, C.; Barta-Boszormenyi, A.; Kahlert, S.; Zuschratter, W.; Faber-Zuschratter, H.; Reinhardt, N.; Ponsuksili, S.; Wimmers, K.; Diesing, A.K.; Rothkötter, H.J. Comparing two intestinal porcine epithelial cell lines (IPECs): Morphological differentiation, function and metabolism. PLoS ONE 2015, 10, e0132323. [Google Scholar] [CrossRef] [PubMed]
- Abouzied, M.M.; Azcona, J.I.; Braselton, W.E.; Pestka, J.J. Immunochemical assessment of mycotoxins in 1989 grain foods: Evidence for deoxynivalenol (vomitoxin) contamination. Appl. Environ. Microbiol. 1991, 57, 672–677. [Google Scholar] [PubMed]
- Maresca, M.; Mahfoud, R.; Garmy, N.; Fantini, J. The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells. J. Nutr. 2002, 132, 2723–2731. [Google Scholar] [PubMed]
- Diesing, A.K.; Nossol, C.; Danicke, S.; Walk, N.; Post, A.; Kahlert, S.; Rothkötter, H.J.; Kluess, J. Vulnerability of polarised intestinal porcine epithelial cells to mycotoxin deoxynivalenol depends on the route of application. PLoS ONE 2011, 6, e17472. [Google Scholar] [CrossRef] [PubMed]
- Bianco, G.; Fontanella, B.; Severino, L.; Quaroni, A.; Autore, G.; Marzocco, S. Nivalenol and deoxynivalenol affect rat intestinal epithelial cells: A concentration related study. PLoS ONE 2012, 7, e52051. [Google Scholar] [CrossRef] [PubMed]
- Awad, W.A.; Aschenbach, J.R.; Setyabudi, F.M.; Razzazi-Fazeli, E.; Boehm, J.; Zentek, J. In vitro effects of deoxynivalenol on small intestinal d-glucose uptake and absorption of deoxynivalenol across the isolated jejunal epithelium of laying hens. Poult. Sci. 2007, 86, 15–20. [Google Scholar] [CrossRef] [PubMed]
- Pinton, P.; Nougayrede, J.P.; Del Rio, J.C.; Moreno, C.; Marin, D.E.; Ferrier, L.; Bracarense, A.P.; Kolf-Clauw, M.; Oswald, I.P. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression. Toxicol. Appl. Pharmacol. 2009, 237, 41–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maresca, M. From the gut to the brain: Journey and pathophysiological effects of the food-associated trichothecene mycotoxin deoxynivalenol. Toxins 2013, 5, 784–820. [Google Scholar] [CrossRef] [PubMed]
- Zhou, H.R.; Islam, Z.; Pestka, J.J. Induction of competing apoptotic and survival signaling pathways in the macrophage by the ribotoxic trichothecene deoxynivalenol. Toxicol. Sci. 2005, 87, 113–122. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Ye, Y.; Deng, L.; Ma, H.; Fan, X.; Zhang, Y.; Yan, H.; Deng, X.; Li, Y.; Ma, Y. Gene expression profiling analysis of deoxynivalenol-induced inhibition of mouse thymic epithelial cell proliferation. Environ. Toxicol. Pharmacol. 2013, 36, 557–566. [Google Scholar] [CrossRef] [PubMed]
- Bensassi, F.; Gallerne, C.; El Dein, O.S.; Lemaire, C.; Hajlaoui, M.R.; Bacha, H. Involvement of mitochondria-mediated apoptosis in deoxynivalenol cytotoxicity. Food Chem. Toxicol. 2012, 50, 1680–1689. [Google Scholar] [CrossRef] [PubMed]
- Bensassi, F.; El Golli-Bennour, E.; Abid-Essefi, S.; Bouaziz, C.; Hajlaoui, M.R.; Bacha, H. Pathway of deoxynivalenol-induced apoptosis in human colon carcinoma cells. Toxicology 2009, 264, 104–109. [Google Scholar] [CrossRef] [PubMed]
- Fernandes-Alnemri, T.; Litwack, G.; Alnemri, E.S. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J. Biol. Chem. 1994, 269, 30761–30764. [Google Scholar] [PubMed]
- Guan, X.H.; Fu, Q.C.; Shi, D.; Bu, H.L.; Song, Z.P.; Xiong, B.R.; Shu, B.; Xiang, H.B.; Xu, B.; Manyande, A.; et al. Activation of spinal chemokine receptor CXCR3 mediates bone cancer pain through an Akt-ERK crosstalk pathway in rats. Exp. Neurol. 2015, 263, 39–49. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.J.; Oh, J.E.; Kim, S.W.; Chun, Y.J.; Kim, M.Y. Ceramide induces p38 MAPK-dependent apoptosis and Bax translocation via inhibition of Akt in HL-60 cells. Cancer Lett. 2008, 260, 88–95. [Google Scholar] [CrossRef] [PubMed]
- Pim, D.; Massimi, P.; Dilworth, S.M.; Banks, L. Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A. Oncogene 2005, 24, 7830–7838. [Google Scholar] [CrossRef] [PubMed]
- Solit, D.B.; Basso, A.D.; Olshen, A.B.; Scher, H.I.; Rosen, N. Inhibition of heat shock protein 90 function down-regulates Akt kinase and sensitizes tumors to taxol. Cancer Res. 2003, 63, 2139–2144. [Google Scholar] [PubMed]
- Cardone, M.H.; Roy, N.; Stennicke, H.R.; Salvesen, G.S.; Franke, T.F.; Stanbridge, E.; Frisch, S.; Reed, J.C. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998, 282, 1318–1321. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Tang, N.; Hadden, T.J.; Rishi, A.K. Akt, FoxO and regulation of apoptosis. BBA Mol. Cell Res. 2011, 1813, 1978–1986. [Google Scholar] [CrossRef] [PubMed]
- Shaulian, E.; Karin, M. Ap-1 as a regulator of cell life and death. Nat. Cell Biol. 2002, 4, 131–136. [Google Scholar] [CrossRef] [PubMed]
- Gupta, S.; Campbell, D.; Derijard, B.; Davis, R.J. Transcription factor ATF2 regulation by the JNK signal transduction pathway. Science 1995, 267, 389–393. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Liu, Q.; Ihsan, A.; Huang, L.; Dai, M.; Hao, H.; Cheng, G.; Liu, Z.; Wang, Y.; Yuan, Z. JAK/STAT pathway plays a critical role in the proinflammatory gene expression and apoptosis of RAW264.7 cells induced by trichothecenes as DON and T-2 toxin. Toxicol. Sci. 2012, 127, 412–424. [Google Scholar] [CrossRef] [PubMed]
- Kim, H.S.; Lee, M.S. STAT1 as a key modulator of cell death. Cell Signal. 2007, 19, 454–465. [Google Scholar] [CrossRef] [PubMed]
- Stephanou, A.; Latchman, D.S. Opposing actions of STAT-1 and STAT-3. Growth Factors 2005, 23, 177–182. [Google Scholar] [CrossRef] [PubMed]
- Horvath, C.M.; Stark, G.R.; Kerr, I.M.; Darnell, J.E. Interactions between STAT and non-STAT proteins in the interferon-stimulated gene factor 3 transcription complex. Mol. Cell. Biol. 1996, 16, 6957–6964. [Google Scholar] [CrossRef] [PubMed]
- Liu, B.; Liao, J.Y.; Rao, X.P.; Kushner, S.A.; Chung, C.D.; Chang, D.D.; Shuai, K. Inhibition of Stat1-mediated gene activation by PIAS1. Proc. Natl. Acad. Sci. USA 1998, 95, 10626–10631. [Google Scholar] [CrossRef] [PubMed]
- González-Mariscal, L.; Tapia, R.; Chamorro, D. Crosstalk of tight junction components with signaling pathways. BBA Biomembr. 2008, 1778, 729–756. [Google Scholar] [CrossRef] [PubMed]
- Heyman, M.; Abed, J.; Lebreton, C.; Cerf-Bensussan, N. Intestinal permeability in coeliac disease: Insight into mechanisms and relevance to pathogenesis. Gut 2012, 61, 1355–1364. [Google Scholar] [CrossRef] [PubMed]
- Awad, W.A.; Zentek, J. The feed contaminant deoxynivalenol affects the intestinal barrier permeability through inhibition of protein synthesis. Arch. Toxicol. 2014, 89, 961–965. [Google Scholar] [CrossRef] [PubMed]
- Matter, K.; Balda, M.S. Signalling to and from tight junctions. Nat. Rev. Mol. Cell Biol. 2003, 4, 225–236. [Google Scholar] [CrossRef] [PubMed]
- Hokari, R; Lee, H; Crawley, S.C; Yang, S.C; Gum, J.R; Miura, S; Kim, Y.S. Vasoactive intestinal peptide upregulates MUC2 intestinal mucin via CREB/ATF1. Am. J. Physiol. Gastrointest. Liver Physiol. 2005, 289, 949–959. [Google Scholar] [CrossRef] [PubMed]
- Jung, T.H.; Park, J.H.; Jeon, W.M.; Han, K.S. Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretion and MAPK signaling pathway. Nutr. Res. Pract. 2015, 9, 343–349. [Google Scholar] [CrossRef] [PubMed]
- Yang, R.; Harada, T.; Li, J.; Uchiyama, T.; Han, Y.; Englert, J.A.; Fink, M.P. Bile modulates intestinal epithelial barrier function via an extracellular signal related kinase 1/2 dependent mechanism. Intensive Care Med. 2005, 31, 709–717. [Google Scholar] [CrossRef] [PubMed]
- Pinton, P.; Braicu, C.; Nougayrede, J.P.; Laffitte, J.; Taranu, I.; Oswald, I.P. Deoxynivalenol impairs porcine intestinal barrier function and decreases the protein expression of claudin-4 through a mitogen-activated protein kinase-dependent mechanism. J. Nutr. 2010, 140, 1956–1962. [Google Scholar] [CrossRef] [PubMed]
- Banan, A.; Zhang, L.J.; Shaikh, M.; Fields, J.Z.; Choudhary, S.; Forsyth, C.B.; Farhadi, A.; Keshavarzian, A. θ isoform of protein kinase C alters barrier function in intestinal epithelium through modulation of distinct claudin isotypes: A novel mechanism for regulation of permeability. J. Pharmacol. Exp. 2005, 313, 962–982. [Google Scholar] [CrossRef]
- Nunbhakdi-Craig, V.; Machleidt, T.; Ogris, E.; Bellotto, D.; White, C.L.; Sontag, E. Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex. J. Cell Biol. 2002, 158, 967–978. [Google Scholar] [CrossRef] [PubMed]
- Ivanov, A.I.; McCall, I.C.; Parkos, C.A.; Nusrat, A. Role for actin filament turnover and a myosin II motor in cytoskeleton-driven disassembly of the epithelial apical junctional complex. Mol. Biol. Cell 2004, 15, 2639–2651. [Google Scholar] [CrossRef] [PubMed]
- Turner, J.R.; Angle, J.M.; Black, E.D.; Joyal, J.L.; Sacks, D.B.; Madara, J.L. PKC-dependent regulation of transepithelial resistance: Roles of MLC and MLC kinase. Am. J. Physiol. Cell Physiol. 1999, 277, 554–562. [Google Scholar]
- Garrido-Urbani, S.; Bradfield, P.F.; Imhof, B.A. Tight junction dynamics: The role of junctional adhesion molecules (JAMs). Cell Tissue Res. 2014, 355, 701–715. [Google Scholar] [CrossRef] [PubMed]
- Pinton, P.; Guzylack-Piriou, L.; Kolf-Clauw, M.; Oswald, I.P. The effect on the intestine of some fungal toxins: The trichothecenes. Curr. Opin. Immunol. 2012, 8, 193–208. [Google Scholar] [CrossRef]
- Wang, Q.Y.; Sun, A.M.; Song, J.; Chen, Y.; Wang, J.D.; Li, C.G. Cytokine tumor necrosis factor alpha induces intestinal epithelial barrier dysfunction. Cytokine 2012, 58, 226–230. [Google Scholar] [CrossRef] [PubMed]
- Wan, L.Y.M.; Woo, C.S.J.; Turner, P.C.; Wan, J.M.F.; El-Nezami, H. Individual and combined effects of Fusarium toxins on the mRNA expression of pro-inflammatory cytokines in swine jejunal epithelial cells. Toxicol. Lett. 2013, 220, 238–246. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, K.S.; Chamaillard, M.; Ogura, Y.; Henegariu, O.; Inohara, N.; Nuñez, G.; Flavell, R.A. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 2005, 307, 731–734. [Google Scholar] [CrossRef] [PubMed]
- Tao, F.; Qian, C.; Guo, W.; Luo, Q.; Xu, Q.; Sun, Y. Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin. Biochem. Pharmacol. 2013, 85, 798–807. [Google Scholar] [CrossRef] [PubMed]
- Cano, P.M.; Seeboth, J.; Meurens, F.; Cognie, J.; Abrami, R.; Oswald, I.P.; Guzylack-Piriou, L. Deoxynivalenol as a new factor in the persistence of intestinal inflammatory diseases: An emerging hypothesis through possible modulation of Th17-mediated response. PLoS ONE 2013, 8, e53647. [Google Scholar] [CrossRef] [PubMed]
- Sumagin, R.; Parkos, C.A. Epithelial adhesion molecules and the regulation of intestinal homeostasis during neutrophil transepithelial migration. Tissue Barriers 2015, 3, e969100. [Google Scholar] [CrossRef] [PubMed]
- Röder, P.V.; Geillinger, K.E.; Zietek, T.S.; Thorens, B.; Koepsell, H.; Daniel, H. The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS ONE 2014, 9, e89977. [Google Scholar] [CrossRef] [PubMed]
- Awad, W.A.; Böhm, J.; Razzazi-Fazeli, E.; Zentek, J. In vitro effects of deoxynivalenol on electrical properties of intestinal mucosa of laying hens. Poult. Sci. 2005, 84, 921–927. [Google Scholar] [CrossRef] [PubMed]
- Castaneda-Sceppa, C.; Subramanian, S.; Castaneda, F. Protein kinase C mediated intracellular signaling pathways are involved in the regulation of sodium-dependent glucose co-transporter SGLT1 activity. J. Cell Biochem. 2010, 109, 1109–1117. [Google Scholar] [CrossRef] [PubMed]
- Schultz, S.G.; Curran, P.F. Coupled transport of sodium and organic solutes. Physiol. Rev. 1970, 50, 637–718. [Google Scholar] [PubMed]
- Kirschner, N.; Rosenthal, R.; Furuse, M.; Moll, I.; Fromm, M.; Brandner, J.M. Contribution of tight junction proteins to ion, macromolecule, and water barrier in keratinocytes. J. Investig. Dermatol. 2013, 133, 1161–1169. [Google Scholar] [CrossRef] [PubMed]
- Wada, M.; Tamura, A.; Takahashi, N.; Tsukita, S. Loss of claudins 2 and 15 from mice causes defects in paracellular Na+ flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterology 2013, 144, 369–380. [Google Scholar] [CrossRef] [PubMed]
- Bouhet, S.; Hourcade, E.; Loiseau, N.; Fikry, A.; Martinez, S.; Roselli, M.; Galtier, P.; Mengheri, E.; Oswald, I.P. The mycotoxin fumonisin B1 alters the proliferation and the barrier function of porcine intestinal epithelial cells. Toxicol. Sci. 2004, 77, 165–171. [Google Scholar] [CrossRef] [PubMed]
- Bouhet, S.; Le Dorze, E.; Peres, S.; Fairbrother, J.M.; Oswald, I.P. Mycotoxin fumonisin B1 selectively down-regulates the basal IL-8 expression in pig intestine: In vivo and in vitro studies. Food Chem. Toxicol. 2006, 44, 1768–1773. [Google Scholar] [CrossRef] [PubMed]
- Trinder, P. Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen. J. Clin. Pathol. 1969, 22, 158–161. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.Q.; Shu, G.; Zhu, X.T.; Wang, L.N.; Fu, Q.; Hou, L.J.; Wang, S.B.; Gao, P.; Xi, Q.Y.; Zhang, Y.L.; et al. Isolation and characterization of porcine circumvallate papillae cells. Acta Histochem. 2014, 116, 1313–1322. [Google Scholar] [CrossRef] [PubMed]
- Wisniewski, J.R.; Zougman, A.; Nagaraj, N.; Mann, M. Universal sample preparation method for proteome analysis. Nat. Methods 2009, 6, 359–362. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Xu, H.; Chen, H.; Xie, J.; Shi, M.; Shen, B.; Deng, X.; Liu, C.; Zhan, X.; Peng, C. Proteomic analysis of solid pseudopapillary tumor of the pancreas reveals dysfunction of the endoplasmic reticulum protein processing pathway. Mol. Cell. Proteom. 2014, 13, 2593–2603. [Google Scholar] [CrossRef] [PubMed]
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, Z.-Q.; Wang, S.-B.; Wang, R.-G.; Zhang, W.; Wang, P.-L.; Su, X.-O. Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells. Toxins 2016, 8, 270. https://doi.org/10.3390/toxins8100270
Zhang Z-Q, Wang S-B, Wang R-G, Zhang W, Wang P-L, Su X-O. Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells. Toxins. 2016; 8(10):270. https://doi.org/10.3390/toxins8100270
Chicago/Turabian StyleZhang, Zhi-Qi, Song-Bo Wang, Rui-Guo Wang, Wei Zhang, Pei-Long Wang, and Xiao-Ou Su. 2016. "Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells" Toxins 8, no. 10: 270. https://doi.org/10.3390/toxins8100270
APA StyleZhang, Z. -Q., Wang, S. -B., Wang, R. -G., Zhang, W., Wang, P. -L., & Su, X. -O. (2016). Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells. Toxins, 8(10), 270. https://doi.org/10.3390/toxins8100270