PUBLICATION

Activation of Nrf2 at Critical Windows of Development Alters Tissue-Specific Protein S-Glutathionylation in the Zebrafish (Danio rerio) Embryo

Authors: Marques, E.S., Severance, E.G., Arsenault, P., Zahn, S.M., Timme-Laragy, A.R.
ID: ZDB-PUB-240901-5
Date: 2024
Source: Antioxidants (Basel, Switzerland) 13(8): (Journal)
Registered Authors
Keywords: Danio rerio, Nrf2, glutathionylation, liver, pancreas, redox stress, sulforaphane (SFN), tert-butylhydroquinone (tBHQ)
MeSH Terms: none
PubMed: 39199250 Full text @ Antioxidants (Basel)

Abstract

Activation of Nrf2-the master regulator of antioxidative response-at different stages of embryonic development has been shown to result in changes in gene expression, but the tissue-specific and downstream effects of Nrf2 activation during development remain unclear. This work seeks to elucidate the tissue-specific Nrf2 cellular localization and the downstream changes in protein S-glutathionylation during critical windows of zebrafish (Danio rerio) development. Wild-type and mutant zebrafish embryos with a loss-of-function mutation in Nrf2a were treated with two canonical activators, sulforaphane (SFN; 40 µM) or tert-butylhydroquinone (tBHQ; 1 µM), for 6 h at either pharyngula, hatching, or the protruding-mouth stage. Nrf2a protein and S-glutathionylation were visualized in situ using immunohistochemistry. At the hatching stage, Nrf2a protein levels were decreased with SFN, but not tBHQ, exposure. Exposure to both activators, however, decreased downstream S-glutathionylation. Stage- and tissue-specific differences in Nrf2a protein and S-glutathionylation were identified in the pancreatic islet and liver. Protein S-glutathionylation in Nrf2a mutant fish was increased in the liver by both activators, but not the islets, indicating a tissue-specific and Nrf2a-dependent dysregulation. This work demonstrates that critical windows of exposure and Nrf2a activity may influence redox homeostasis and highlights the importance of considering tissue-specific outcomes and sensitivity in developmental redox biology.

Genes / Markers

Figures