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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...

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Autores principales: Yoo, Hong Sik, Rodriguez, Adrienne, You, Dongjoo, Lee, Rebecca A., Cockrum, Michael A., Grimes, Jack A., Wang, Jen-Chywan, Kang, Sona, Napoli, Joseph L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
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.
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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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