Multi-omic analysis of zebrafish models of acute organophosphorus poisoning with different severity
| Autor: | Benjamin Piña, Mark A. Arick, Tamar Ziv, Natàlia Garcia-Reyero, Cristian Gómez-Canela, Shani Ben-Lulu, Melissa Faria, Demetrio Raldúa, Eva Prats, Arie Admon |
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| Přispěvatelé: | European Research Council, Prats, Eva, Raldúa, Demetrio, Prats, Eva [0000-0001-7838-2027], Raldúa, Demetrio [0000-0001-5256-1641] |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Status epilepticus Brain damage Toxicology Bioinformatics Transcriptome 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics medicine Zebrafish biology business.industry biology.organism_classification Omics Multiomics Acetylcholinesterase 3. Good health Animal models 030104 developmental biology Acute organophosphorus poisoning chemistry Unfolded protein response medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1096-0929 |
| Popis: | Organophosphorus compounds are acetylcholinesterase inhibitors used as pesticides and chemical warfare nerve agents. Acute organophosphorus poisoning (acute OPP) affects 3 million people, with 300 000 deaths annually worldwide. Severe acute OPP effects include overstimulation of cholinergic neurons, seizures, status epilepticus, and finally, brain damage. In a previous study, we developed 3 different chemical models of acute OPP in zebrafish larvae. To elucidate the complex pathophysiological pathways related to acute OPP, we used integrative omics (proteomic, transcriptomics, and metabolomics) on these 3 animal models. Our results show that these stochastic, apparently disparate morphological phenotypes can result from almost linear concentration-response variations in molecular levels. Results from the multiomics analysis strongly suggest that endoplasmic reticulum stress might play a central role in the pathophysiology of severe acute OPP, emphasizing the urgent need of further research on this molecular pathway. Endoplasmic reticulum stress could be an important therapeutic target to be included in the treatment of patients with severe acute OPP. NATO SfP project MD.SFPP 984777 (D.R.); the European Research Council under European Union’s Seven Framework Programme (FP/2007–2013)/ERC Grant Agreement No. 320737; the Spanish Government (CTM2017-83242-R and CTM2015-65691-R). M.F. acknowledges the financial support from the Government of Catalonia through a Beatriu de Pinos fellowship (2016 BP-B 00233) |
| Databáze: | OpenAIRE |
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