Activation of Nrf2 at Critical Windows of Development Alters Tissue-Specific Protein <i>S</i>-Glutathionylation in the Zebrafish (<i>Danio rerio</i>) Embryo
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...
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| Main Authors: | , , , , |
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| Format: | Book |
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MDPI AG,
2024-08-01T00:00:00Z.
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| Summary: | 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 <i>S</i>-glutathionylation during critical windows of zebrafish (<i>Danio rerio</i>) 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 <i>S</i>-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 <i>S</i>-glutathionylation. Stage- and tissue-specific differences in Nrf2a protein and <i>S</i>-glutathionylation were identified in the pancreatic islet and liver. Protein <i>S</i>-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. |
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| Item Description: | 10.3390/antiox13081006 2076-3921 |