Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids

Kinser, Shawn; Li, Maioxing; Jia, Qunshan; Pestka, James J.

doi:10.1016/j.jnutbio.2004.10.003

Cited by 23 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MIP-2, MCP-1) and other inflammatory-related genes that are reported to be regulated on the transcription level (e.g. CD40, TLR2) (Kinser et al , 2005; He et al , 2012). The AKT and AMPK pathways also converge and regulate the activity of mTOR pathway that controls translation via p70S6K and eIF4E, with the latter also being modulated by MAPK.…”

Section: Resultsmentioning

confidence: 99%

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

Pan

Whitten

et al. 2013

Toxicology and Applied Pharmacology

Self Cite

View full text Add to dashboard Cite

Deoxynivalenol (DON), a trichothecenemycotoxin produced by Fusarium that commonly contaminates food, is capable of activating mononuclear phagocytes of the innate immune system via a process termed the ribotoxic stress response (RSR). To encapture global signaling events mediating RSR, we quantified the early temporal (≤30 min) phosphoproteome changes that occurred in RAW 264.7 murine macrophage during exposure to a toxicologically relevant concentration of DON (250 ng/mL). Large-scale phosphoproteomic analysis employing stable isotope labeling of amino acids in cell culture (SILAC) in conjunction with titanium dioxide chromatography revealed that DON significantly upregulated or downregulated phosphorylation of 188 proteins at both known and yet-to-be functionally characterized phosphosites. DON-induced RSR is extremely complex and goes far beyond its prior known capacity to inhibit translation and activate MAPKs. Transcriptional regulation was the main target during early DON-induced RSR, covering over 20 percent of the altered phosphoproteins as indicated by Gene Ontology annotation and including transcription factors/cofactors and epigenetic modulators. Other biological processes impacted included cell cycle, RNA processing, translation, ribosome biogenesis, monocyte differentiation and cytoskeleton organization. Some of these processes could be mediated by signaling networks involving MAPK-, NFκB-, AKT- and AMPK-linked pathways. Fuzzy c-means clustering revealed that DON-regulated phosphosites could be discretely classified with regard to the kinetics of phosphorylation/dephosphorylation. The cellular response networks identified provide a template for further exploration of the mechanisms of trichothecenemycotoxins and other ribotoxins, and ultimately, could contribute to improved mechanism-based human health risk assessment.

show abstract

Section: Resultsmentioning

confidence: 99%

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

Pan

Whitten

et al. 2013

Toxicology and Applied Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…None of experimental diets exceeded the detection limit of 10-mg deoxynivalenol per kg feed. The mice were fed the AIN-93G diet with or without 1% GOS for 2 wk before being challenged with deoxynivalenol, given by oral gavage at a dose of 25-mg/kg body weight in 200-ml sterile PBS (29)(30)(31). Control mice received 200-ml sterile PBS.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

Galacto-oligosaccharides Protect the Intestinal Barrier by Maintaining the Tight Junction Network and Modulating the Inflammatory Responses after a Challenge with the Mycotoxin Deoxynivalenol in Human Caco-2 Cell Monolayers and B6C3F1 Mice

Akbari

Braber

Alizadeh

et al. 2015

The Journal of Nutrition

119

103

View full text Add to dashboard Cite

show abstract

“…Numerous immunotoxicity studies are cited in the JECFA monograph under the following topics: altered host resistance and humoral and cell-mediated responses, altered serum IgA levels, IgA-associated nephropathy, cytokine expression, and apoptosis in lymphoid tissue. Copious studies have since been conducted (Gray & Pestka, 2007; Chung et al ., 2003; Kinser et al ., 2005; Pestka & Zhou, 2000; Sugita-Konishi & Pestka, 2001; Uzarski et al ., 2003; Wong et al ., 2002; Yang et al ., 2000). Additional in vitro studies showed that DON inhibited nuclear protein binding to NRE-A, an IL-2 promoter negative regulatory element, in murine lymphoma EL-4 T cells, induced cytotoxicity and apoptosis in WEHI-231 B cells, induced p38 activation, and increased IL-8 production (Zhou et al ., 2005).…”

Section: Trichothecenes and Deoxynivalenolmentioning

confidence: 99%

Deoxynivalenol and its toxicity

Šobrová

Adam²,

Vasatkova³

et al. 2010

Interdisciplinary Toxicology

418

293

View full text Add to dashboard Cite

Deoxynivalenol (DON) is one of several mycotoxins produced by certain Fusarium species that frequently infect corn, wheat, oats, barley, rice, and other grains in the field or during storage. The exposure risk to human is directly through foods of plant origin (cereal grains) or indirectly through foods of animal origin (kidney, liver, milk, eggs). It has been detected in buckwheat, popcorn, sorgum, triticale, and other food products including flour, bread, breakfast cereals, noodles, infant foods, pancakes, malt and beer. DON affects animal and human health causing acute temporary nausea, vomiting, diarrhea, abdominal pain, headache, dizziness, and fever. This review briefly summarizes toxicities of this mycotoxin as well as effects on reproduction and their antagonistic and synergic actions.

show abstract

Truncated deoxynivalenol-induced splenic immediate early gene response in mice consuming (n-3) polyunsaturated fatty acids

Cited by 23 publications

References 39 publications

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

Global protein phosphorylation dynamics during deoxynivalenol-induced ribotoxic stress response in the macrophage

Galacto-oligosaccharides Protect the Intestinal Barrier by Maintaining the Tight Junction Network and Modulating the Inflammatory Responses after a Challenge with the Mycotoxin Deoxynivalenol in Human Caco-2 Cell Monolayers and B6C3F1 Mice

Deoxynivalenol and its toxicity

Contact Info

Product

Resources

About