Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System
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 remarkab...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/7/6804 |
| _version_ | 1797607720489058304 |
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| author | Lorenzo Badenetti Rosa Manzoli Michela Rubin Giorgio Cozza Enrico Moro |
| author_facet | Lorenzo Badenetti Rosa Manzoli Michela Rubin Giorgio Cozza Enrico Moro |
| author_sort | Lorenzo Badenetti |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T05:33:41Z |
| format | Article |
| id | doaj.art-45417cae1315410a8299ea296c3d5ccd |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:33:41Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-45417cae1315410a8299ea296c3d5ccd2023-11-17T16:56:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01247680410.3390/ijms24076804Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter SystemLorenzo Badenetti0Rosa Manzoli1Michela Rubin2Giorgio Cozza3Enrico Moro4Department of Women’s and Children’s Health, University of Padova, I-35128 Padova, ItalyDepartment of Molecular Medicine, University of Padova, I-35121 Padova, ItalyDepartment of Molecular Medicine, University of Padova, I-35121 Padova, ItalyDepartment of Molecular Medicine, University of Padova, I-35121 Padova, ItalyDepartment of Molecular Medicine, University of Padova, I-35121 Padova, ItalyAmong 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.https://www.mdpi.com/1422-0067/24/7/6804Nrf2zebrafishtransgenic reporterdrug |
| spellingShingle | Lorenzo Badenetti Rosa Manzoli Michela Rubin Giorgio Cozza Enrico Moro Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System International Journal of Molecular Sciences Nrf2 zebrafish transgenic reporter drug |
| title | Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System |
| title_full | Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System |
| title_fullStr | Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System |
| title_full_unstemmed | Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System |
| title_short | Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System |
| title_sort | monitoring nrf2 are pathway activity with a new zebrafish reporter system |
| topic | Nrf2 zebrafish transgenic reporter drug |
| url | https://www.mdpi.com/1422-0067/24/7/6804 |
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