Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets
The transcription factor NFE2L2 (Nuclear Factor, Erythroid 2-Like 2, or NRF2) plays a key role in maintaining the redox state within cells. Characterization of this pathway has extended to fish, most notably zebrafish (Danio rerio), in which two paralogs of the transcription factor exist: Nrf2a, an...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-10-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231716300568 |
| _version_ | 1828487661826867200 |
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| author | Richard Ramsden Evan P. Gallagher |
| author_facet | Richard Ramsden Evan P. Gallagher |
| author_sort | Richard Ramsden |
| collection | DOAJ |
| description | The transcription factor NFE2L2 (Nuclear Factor, Erythroid 2-Like 2, or NRF2) plays a key role in maintaining the redox state within cells. Characterization of this pathway has extended to fish, most notably zebrafish (Danio rerio), in which two paralogs of the transcription factor exist: Nrf2a, an activator, and Nrf2b, a negative regulator during embryogenesis. Only one ARE target has been thoroughly delineated in zebrafish, and this deviated from the canonical sequence derived from studies in mammals. In general, the mechanistic pathway has not been characterized in non-model aquatic organisms that are commonly exposed to environmental pollutants. The current study compares the zebrafish paralogs to those found in a non-model teleost, the ecologically important salmonid, Oncorhnychus kisutch (coho salmon). Two salmon paralogs, Nrf2A and -2B, described here were found to possess only slightly greater identity between one another (84% of amino acids) than to the singleton ortholog of the esocid Esox lucius (80–82%), the nearest non-salmonid outgroup. Unlike one of the zebrafish forms, each is a strong activating factor based on sequence homology and in vitro testing. To uncover functional target AREs in coho, promoter flanking sequences were isolated for five genes that protect cells against oxidative stress: heme oxygenase 1, peroxiredoxin 1, glutamate-cysteine ligase, and the glutathione S-transferases pi and rho (hmox1, prdx1, gclc, gstp, and gstr). All except gstr had functional elements and all fit the standard mammalian-derived canonical sequence, unlike the motif found in zebrafish gstp. Expression studies demonstrate the presence of both Nrf2 paralogs in multiple organs, although in differing ratios. Collectively, our findings extend the conservation of Nrf2 and the ARE to salmonids, and should help inform future work in teleosts on mechanisms of redox control, as well as responsiveness of this pathway and its downstream antioxidant gene targets to chemical exposures in the environment. |
| first_indexed | 2024-12-11T09:54:34Z |
| format | Article |
| id | doaj.art-553eee7a33af4b97b1af2ef7b97a40ac |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-11T09:54:34Z |
| publishDate | 2016-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-553eee7a33af4b97b1af2ef7b97a40ac2022-12-22T01:12:18ZengElsevierRedox Biology2213-23172016-10-019C11412310.1016/j.redox.2016.07.001Dual NRF2 paralogs in Coho salmon and their antioxidant response element targetsRichard RamsdenEvan P. GallagherThe transcription factor NFE2L2 (Nuclear Factor, Erythroid 2-Like 2, or NRF2) plays a key role in maintaining the redox state within cells. Characterization of this pathway has extended to fish, most notably zebrafish (Danio rerio), in which two paralogs of the transcription factor exist: Nrf2a, an activator, and Nrf2b, a negative regulator during embryogenesis. Only one ARE target has been thoroughly delineated in zebrafish, and this deviated from the canonical sequence derived from studies in mammals. In general, the mechanistic pathway has not been characterized in non-model aquatic organisms that are commonly exposed to environmental pollutants. The current study compares the zebrafish paralogs to those found in a non-model teleost, the ecologically important salmonid, Oncorhnychus kisutch (coho salmon). Two salmon paralogs, Nrf2A and -2B, described here were found to possess only slightly greater identity between one another (84% of amino acids) than to the singleton ortholog of the esocid Esox lucius (80–82%), the nearest non-salmonid outgroup. Unlike one of the zebrafish forms, each is a strong activating factor based on sequence homology and in vitro testing. To uncover functional target AREs in coho, promoter flanking sequences were isolated for five genes that protect cells against oxidative stress: heme oxygenase 1, peroxiredoxin 1, glutamate-cysteine ligase, and the glutathione S-transferases pi and rho (hmox1, prdx1, gclc, gstp, and gstr). All except gstr had functional elements and all fit the standard mammalian-derived canonical sequence, unlike the motif found in zebrafish gstp. Expression studies demonstrate the presence of both Nrf2 paralogs in multiple organs, although in differing ratios. Collectively, our findings extend the conservation of Nrf2 and the ARE to salmonids, and should help inform future work in teleosts on mechanisms of redox control, as well as responsiveness of this pathway and its downstream antioxidant gene targets to chemical exposures in the environment.http://www.sciencedirect.com/science/article/pii/S2213231716300568Nuclear factor erythroid 2-like 2Nrf2Antioxidant response elementCoho salmonParalog |
| spellingShingle | Richard Ramsden Evan P. Gallagher Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets Redox Biology Nuclear factor erythroid 2-like 2 Nrf2 Antioxidant response element Coho salmon Paralog |
| title | Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets |
| title_full | Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets |
| title_fullStr | Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets |
| title_full_unstemmed | Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets |
| title_short | Dual NRF2 paralogs in Coho salmon and their antioxidant response element targets |
| title_sort | dual nrf2 paralogs in coho salmon and their antioxidant response element targets |
| topic | Nuclear factor erythroid 2-like 2 Nrf2 Antioxidant response element Coho salmon Paralog |
| url | http://www.sciencedirect.com/science/article/pii/S2213231716300568 |
| work_keys_str_mv | AT richardramsden dualnrf2paralogsincohosalmonandtheirantioxidantresponseelementtargets AT evanpgallagher dualnrf2paralogsincohosalmonandtheirantioxidantresponseelementtargets |