Evidence map›Paper›PMID 22491426›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2012

Targets and intracellular signaling mechanisms for deoxynivalenol-induced ribosomal RNA cleavage.

Kaiyu He, Hui-Ren Zhou, James J Pestka

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 51 citations in OpenAlex.

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  19. Early phosphoproteomic changes in the mouse spleen during deoxynivalenol-induced ribotoxic stress.Toxicological sciences : an official journal of the Society of Toxicology · 2013
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Kaiyu HeDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824-1224, USA.
Hui-Ren Zhou
James J Pestka
Michigan State University · USLaboratoire d’immunologie intégrative du cancer · FR

Funding

Trichothecene Toxicity and the Ribotoxic Stress ResponseR01ES003358 · NIEHS · MICHIGAN STATE UNIVERSITY · PI PESTKA, JAMES J · 1985 to 2012
$3.3M
Mechanisms of Trichothecene ToxicityR56ES003358 · NIEHS · MICHIGAN STATE UNIVERSITY · PI PESTKA, JAMES J · 2005 to 2005
$113k
NIEHS NIH HHS ES003358NIEHS NIH HHS R01 ES003358NIEHS NIH HHS R56 ES003358
6 · The paper itself

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.

Indexed as

AnimalsApoptosisBlotting, NorthernCaspase InhibitorsCaspasesCell LineCysteine Proteinase InhibitorsDose-Response Relationship, DrugeIF-2 KinaseElectrophoresis, CapillaryEnzyme ActivationFlow CytometryMacrophagesMicep38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsCaspase InhibitorsCaspasesCysteine Proteinase InhibitorsdeoxynivalenoleIF-2 Kinasep38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsProto-Oncogene Proteins c-hckRNA, Ribosomal, 18SRNA, Ribosomal, 28STrichothecenesTumor Suppressor Protein p53

Identifiers

PMID22491426
PMCPMC3355321
OpenAlexW2103509661

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.