ArticleToxicological sciences : an official journal of the Society of Toxicology2012
Targets and intracellular signaling mechanisms for deoxynivalenol-induced ribosomal RNA cleavage.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
- Trichothecene mycotoxin-induced ribotoxic stress activates histone gene transcription.Archives of toxicology · 2026Article
- Ribosomal RNA Degradation (RNA Disruption) in Tumour Cells: Mechanistic Insights and Potential Clinical Utility.Cancers · 2025Review
- Leveraging Xenobiotic-Responsive Cancer Stemness in Cell Line-Based Tumoroids for Evaluating Chemoresistance: A Proof-of-Concept Study on Environmental Susceptibility.International journal of molecular sciences · 2024Article
- Diverse mycotoxin threats to safe food and feed cereals.Essays in biochemistry · 2023Review
- Effects of Deoxynivalenol and Fumonisins Fed in Combination to Beef Cattle: Immunotoxicity and Gene Expression.Toxins · 2021Article
- In Vitro Assay of Translation Inhibition by Trichothecenes Using a Commercially Available System.Toxins · 2021Article
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
- Mycotoxin Deoxynivalenol Has Different Impacts on Intestinal Barrier and Stem Cells by Its Route of Exposure.Toxins · 2020Article
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- RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.BMC cancer · 2016Article
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- A novel Peptide-binding motifs inference approach to understand deoxynivalenol molecular toxicity.Toxins · 2015Review
- Reduced susceptibility to Fusarium head blight in Brachypodium distachyon through priming with the Fusarium mycotoxin deoxynivalenol.Molecular plant pathology · 2015Article
- The Food Contaminant Mycotoxin Deoxynivalenol Inhibits the Swallowing Reflex in Anaesthetized Rats.PloS one · 2015Article
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- Dynamic changes in ribosome-associated proteome and phosphoproteome during deoxynivalenol-induced translation inhibition and ribotoxic stress.Toxicological sciences : an official journal of the Society of Toxicology · 2014Article
- Ribosomal alteration-derived signals for cytokine induction in mucosal and systemic inflammation: noncanonical pathways by ribosomal inactivation.Mediators of inflammation · 2014Review
- Early phosphoproteomic changes in the mouse spleen during deoxynivalenol-induced ribotoxic stress.Toxicological sciences : an official journal of the Society of Toxicology · 2013Article
- Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The trichothecene mycotoxin deoxynivalenol (DON), a known translational inhibitor, induces ribosomal RNA (rRNA) cleavage. Here, we characterized this process relative to (1) specific 18S and 28S ribosomal RNA cleavage sites and (2) identity of specific upstream signaling elements in this pathway. Capillary electrophoresis indicated that DON at concentrations as low as 200 ng/ml evoked selective rRNA cleavage after 6 h and that 1000 ng/ml caused cleavage within 2 h. Northern blot analysis revealed that DON exposure induced six rRNA cleavage fragments from 28S rRNA and five fragments from 18S rRNA. When selective kinase inhibitors were used to identify potential upstream signals, RNA-activated protein kinase (PKR), hematopoietic cell kinase (Hck), and p38 were found to be required for rRNA cleavage, whereas c-Jun N-terminal kinase and extracellular signal-regulated kinase were not. Furthermore, rRNA fragmentation was suppressed by the p53 inhibitors pifithrin-α and pifithrin-μ as well as the pan caspase inhibitor Z-VAD-FMK. Concurrent apoptosis was confirmed by acridine orange/ethidium bromide staining and flow cytometry. DON activated caspases 3, 8, and 9, thus suggesting the possible coinvolvement of both extrinsic and intrinsic apoptotic pathways in rRNA cleavage. Satratoxin G (SG), anisomycin, and ricin also induced specific rRNA cleavage profiles identical to those of DON, suggesting that ribotoxins might share a conserved rRNA cleavage mechanism. Taken together, DON-induced rRNA cleavage is likely to be closely linked to apoptosis activation and appears to involve the sequential activation of PKR/Hck →p38→p53→caspase 8/9→caspase 3.
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Registered trials
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