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The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription
Retinoic acid (RA) counters insulin’s metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, co...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249609/ https://www.ncbi.nlm.nih.gov/pubmed/35789854 http://dx.doi.org/10.1016/j.isci.2022.104564 |
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author | Yoo, Hong Sik Rodriguez, Adrienne You, Dongjoo Lee, Rebecca A. Cockrum, Michael A. Grimes, Jack A. Wang, Jen-Chywan Kang, Sona Napoli, Joseph L. |
author_facet | Yoo, Hong Sik Rodriguez, Adrienne You, Dongjoo Lee, Rebecca A. Cockrum, Michael A. Grimes, Jack A. Wang, Jen-Chywan Kang, Sona Napoli, Joseph L. |
author_sort | Yoo, Hong Sik |
collection | PubMed |
description | Retinoic acid (RA) counters insulin’s metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-induced CYP26A1 transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppresses CYP26A1 expression, increasing RA’s elimination half-life. Interaction between CCAAT-enhancer-binding protein beta (C/EBPβ) and the major allele of SNP rs2068888 enhances CYP26A1 expression; the minor allele restricts the C/EBPβ effect on CYP26A1. The major and minor alleles associate with impaired human health or reduction in blood triglycerides, respectively. Thus, regulating CYP26A1 transcription contributes to adapting RA to coordinate energy availability with metabolism. These results enhance insight into CYP26A1 effects on RA during changes in energy status and glucocorticoid receptor modification of RAR-regulated gene expression. |
format | Online Article Text |
id | pubmed-9249609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-92496092022-07-03 The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription Yoo, Hong Sik Rodriguez, Adrienne You, Dongjoo Lee, Rebecca A. Cockrum, Michael A. Grimes, Jack A. Wang, Jen-Chywan Kang, Sona Napoli, Joseph L. iScience Article Retinoic acid (RA) counters insulin’s metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-induced CYP26A1 transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppresses CYP26A1 expression, increasing RA’s elimination half-life. Interaction between CCAAT-enhancer-binding protein beta (C/EBPβ) and the major allele of SNP rs2068888 enhances CYP26A1 expression; the minor allele restricts the C/EBPβ effect on CYP26A1. The major and minor alleles associate with impaired human health or reduction in blood triglycerides, respectively. Thus, regulating CYP26A1 transcription contributes to adapting RA to coordinate energy availability with metabolism. These results enhance insight into CYP26A1 effects on RA during changes in energy status and glucocorticoid receptor modification of RAR-regulated gene expression. Elsevier 2022-06-09 /pmc/articles/PMC9249609/ /pubmed/35789854 http://dx.doi.org/10.1016/j.isci.2022.104564 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Yoo, Hong Sik Rodriguez, Adrienne You, Dongjoo Lee, Rebecca A. Cockrum, Michael A. Grimes, Jack A. Wang, Jen-Chywan Kang, Sona Napoli, Joseph L. The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription |
title | The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription |
title_full | The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription |
title_fullStr | The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription |
title_full_unstemmed | The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription |
title_short | The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription |
title_sort | glucocorticoid receptor represses, whereas c/ebpβ can enhance or repress cyp26a1 transcription |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249609/ https://www.ncbi.nlm.nih.gov/pubmed/35789854 http://dx.doi.org/10.1016/j.isci.2022.104564 |
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