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Soman and VX: different effect on cellular signalling
Jaroslav Pejchal, Jan Österreicher, Jiří Kassa, Aleš Tichý, Zuzana Šinkorová, Lenka Zárybnická, Klára Kubelková, Kamil Kuča
Language English Country Czech Republic
NLK
Free Medical Journals
from 2003 to 2013
Freely Accessible Science Journals
from 2003 to 2013
ROAD: Directory of Open Access Scholarly Resources
from 2002
- Keywords
- VX,
- MeSH
- Activating Transcription Factors drug effects MeSH
- Enterocytes drug effects MeSH
- Financing, Organized MeSH
- Histological Techniques methods statistics & numerical data MeSH
- Tumor Suppressor Protein p53 drug effects MeSH
- Oncogene Protein p21(ras) drug effects MeSH
- Organophosphorus Compounds adverse effects MeSH
- Image Processing, Computer-Assisted statistics & numerical data MeSH
- Rats, Wistar MeSH
- ets-Domain Protein Elk-1 drug effects MeSH
- CREB-Binding Protein drug effects MeSH
- Soman adverse effects MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
The purpose of our study was to examine the early expression of p21 and activated transcription factors ATF-2, CREB, Elk-1, p53 after soman and VX poisoning, to throw light on the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were i.m. poisoned by soman (60 μg.kg-1 – 70% LD50) or VX (8 μg.kg-1 – 70% LD50). Samples were taken 4, 24, and 72 hours after poisoning, immunohistochemically stained and phospho-ATF-2Thr-69/71, phospho-CREBSer-133, phospho-Elk-1Ser-383, phospho-p53Ser-15, and protein p21 expressions were measured using computer Image analysis in apical and cryptal enterocytes of the colon transversum. After soman poisoning, we observed an increased phospho-CREB in cryptal enterocytes 4, 24, and 72 h after poisoning, while apical enterocytes expressed increased phospho-CREB only 72 h after intoxication. Phospho-Elk-1 significantly dropped 4 and 24 h after soman poisoning in the cryptal compartment. Activation of ATF-2 and p53 and expression of p21 were not changed 4, 24, and 72 h after soman poisoning. VX poisoning did not change any of measured parameters. Soman and VX showed a different effect on cellular signalling. Soman seems to cause additional effects, which are not related to the basic mechanism of nerve agent-induced toxicity and which temporarily suppress promitotic pathways of proliferating cells and persist in cells during the differentiation process.
References provided by Crossref.org
Obsahuje tabulky
Bibliography, etc.Literatura
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- $a The purpose of our study was to examine the early expression of p21 and activated transcription factors ATF-2, CREB, Elk-1, p53 after soman and VX poisoning, to throw light on the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were i.m. poisoned by soman (60 μg.kg-1 – 70% LD50) or VX (8 μg.kg-1 – 70% LD50). Samples were taken 4, 24, and 72 hours after poisoning, immunohistochemically stained and phospho-ATF-2Thr-69/71, phospho-CREBSer-133, phospho-Elk-1Ser-383, phospho-p53Ser-15, and protein p21 expressions were measured using computer Image analysis in apical and cryptal enterocytes of the colon transversum. After soman poisoning, we observed an increased phospho-CREB in cryptal enterocytes 4, 24, and 72 h after poisoning, while apical enterocytes expressed increased phospho-CREB only 72 h after intoxication. Phospho-Elk-1 significantly dropped 4 and 24 h after soman poisoning in the cryptal compartment. Activation of ATF-2 and p53 and expression of p21 were not changed 4, 24, and 72 h after soman poisoning. VX poisoning did not change any of measured parameters. Soman and VX showed a different effect on cellular signalling. Soman seems to cause additional effects, which are not related to the basic mechanism of nerve agent-induced toxicity and which temporarily suppress promitotic pathways of proliferating cells and persist in cells during the differentiation process.
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