PUBLICATION
Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain
- Authors
- Raldúa, D., Casado, M., Prats, E., Faria, M., Puig-Castellví, F., Pérez, Y., Alfonso, I., Hsu, C.Y., Arick Ii, M.A., Garcia-Reyero, N., Ziv, T., Ben-Lulu, S., Admon, A., Piña, B.
- ID
- ZDB-PUB-200118-2
- Date
- 2020
- Source
- Scientific Reports 10: 312 (Journal)
- Registered Authors
- Piña, Benjamin, Raldúa, Demetrio
- Keywords
- none
- MeSH Terms
-
- Acrylamide/toxicity*
- Animals
- Brain/drug effects
- Brain/metabolism*
- Gene Expression Regulation/drug effects
- Glutathione/metabolism
- Metabolome/drug effects*
- Oxidation-Reduction
- Proteome/analysis
- Proton Magnetic Resonance Spectroscopy
- Thioredoxins/metabolism
- Zebrafish/metabolism*
- Zebrafish Proteins/metabolism
- PubMed
- 31941973 Full text @ Sci. Rep.
Citation
Raldúa, D., Casado, M., Prats, E., Faria, M., Puig-Castellví, F., Pérez, Y., Alfonso, I., Hsu, C.Y., Arick Ii, M.A., Garcia-Reyero, N., Ziv, T., Ben-Lulu, S., Admon, A., Piña, B. (2020) Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain. Scientific Reports. 10:312.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping