Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain
| Autor: | Demetrio Raldúa, Melissa Faria, Ignacio Alfonso, Arie Admon, Chuan-Yu Hsu, Tamar Ziv, Natàlia Garcia-Reyero, Mark A. Arick, Yolanda Pérez, Marta Casado, Shani Ben-Lulu, Eva Prats, Benjamin Piña, Francesc Puig-Castellví |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Raldúa, Demetrio, Casado, Marta, Prats, Eva, Faria, Melissa S., Puig-Castellví, Francesc, Alfonso, Ignacio, Piña, Benjamin, Raldúa, Demetrio [0000-0001-5256-1641], Casado, Marta [0000-0001-9255-0138], Prats, Eva [0000-0001-7838-2027], Faria, Melissa S. [0000-0003-1451-4427], Puig-Castellví, Francesc [0000-0003-1064-9586], Alfonso, Ignacio [0000-0003-0678-0362], Piña, Benjamin [0000-0001-9216-2768] |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteome
Metabolite Proton Magnetic Resonance Spectroscopy Neurotoxic effects lcsh:Medicine Proteomic analysis Toxicology Redox Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gene expression analysis Thioredoxins Metabolomics Animals lcsh:Science Mode of action Zebrafish 030304 developmental biology chemistry.chemical_classification 0303 health sciences Acrylamide Acrylamides Multidisciplinary biology lcsh:R Brain Glutathione Zebrafish Proteins biology.organism_classification chemistry Biochemistry Gene Expression Regulation Thiol Metabolome lcsh:Q Thioredoxin Oxidation-Reduction 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Digital.CSIC. Repositorio Institucional del CSIC instname Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) |
| Popis: | Exposure to acrylamide may lead to different neurotoxic effects in humans and in experimental animals. To gain insights into this poorly understood type of neurotoxicological damage, we used a multi-omic approach to characterize the molecular changes occurring in the zebrafish brain exposed to acrylamide at metabolite, transcript and protein levels. We detected the formation of acrylamide adducts with thiol groups from both metabolites and protein residues, leading to a quasi-complete depletion of glutathione and to the inactivation of different components of the thioredoxin system. We propose that the combined loss-of-function of both redox metabolism-related systems configure a perfect storm that explains many acrylamide neurotoxic effects, like the dysregulation of genes related to microtubules, presynaptic vesicle alteration, and behavioral alterations. We consider that our mechanistical approach may help developing new treatments against the neurotoxic effects of acrylamide and of other neurotoxicants that may share its toxic mode of action. This work was supported by the NATO SfP project MD.SFPP 984777 (D.R., A.A.), the Advanced Grant ERC-2012-AdG-320737 (D.R., B.P., F. P.-C.), the Spanish Government (CTM2017-83242-R, RTI2018-096175-B-I00); D.R., B.P.) and the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation (grant No. 1775/12 to A.A.). M.F. acknowledges financial support from the Beatriu de Pinós programme (grant No. 2016 BP 00233) provided by the Secretariat of Universities and Research department of the Department for Business and Knowledge, Catalan Government. The 500 MHz spectrometer was purchased in part through a Research Infrastructure MINECO-FEDER fund (Grant CSIC13-4E-2076). |
| Databáze: | OpenAIRE |
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