PUBLICATION

Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System

Authors
Badenetti, L., Manzoli, R., Rubin, M., Cozza, G., Moro, E.
ID
ZDB-PUB-230414-57
Date
2023
Source
International Journal of Molecular Sciences   24(7): (Journal)
Registered Authors
Badenetti, Lorenzo, Manzoli, Rosa, Moro, Enrico, Rubin, Michela
Keywords
Nrf2, drug, transgenic reporter, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics
  • Antioxidants/metabolism
  • Humans
  • NF-E2-Related Factor 2*/genetics
  • NF-E2-Related Factor 2*/metabolism
  • Oxidative Stress/genetics
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
  • Zebrafish Proteins/metabolism
PubMed
37047777 Full text @ Int. J. Mol. Sci.
Abstract
Among multiple cytoprotective mechanisms, eukaryotic cells exhibit a complex transcriptional program relying on the Nrf2 transcription factor, which is generally recruited upon biological stressors including oxidative-stress-based cellular insults. The relevance of this master regulator has remarkably emerged in recent years in several research fields such as cancer, inflammatory disorders and age-related neurological diseases. Here, we document the generation and characterization of a novel Nrf2/ARE pathway biosensor fish which exhibits a dynamic spatiotemporal expression profile during the early developmental stages. The transgenic line is responsive to known Nrf2 pathway modulators but also to Edaravone, which direct activity on the Nrf2 pathway has never been documented in a live transgenic fish model. We also show that the reporter is faithfully activated during fin regeneration, and its degree of expression is slightly affected in a glucocerebrosidase (Gba1) morphant zebrafish model. Therefore, this novel transgenic fish may represent a valuable tool to be exploited for the characterization of zebrafish models of human diseases, as well as for primary high-throughput drug screening.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping