Academic Journal
Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes
| العنوان: | Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes |
|---|---|
| المؤلفون: | Ivy, Jessica R., Carter, Roderic N., Zhao, Jin-Feng, Buckley, Charlotte, Urquijo, Helena, Rog-Zielinska, Eva A., Panting, Emma, Hrabalkova, Lenka, Nicholson, Cara, Agnew, Emma J., Kemp, Matthew W., Morton, Nicholson N, Stock, Sarah J., Wyrwoll, Caitlin, Ganley, Ian G., Chapman, Karen E. |
| سنة النشر: | 2021 |
| المجموعة: | University of Strathclyde Glasgow: Strathprints |
| مصطلحات موضوعية: | Therapeutics. Pharmacology |
| الوصف: | The late gestational rise in glucocorticoids contributes to the structural and functional maturation of the perinatal heart. Here, we hypothesized that glucocorticoid action contributes to the metabolic switch in perinatal cardiomyocytes from carbohydrate to fatty acid oxidation. In primary mouse fetal cardiomyocytes, dexamethasone treatment induced expression of genes involved in fatty acid oxidation and increased mitochondrial oxidation of palmitate, dependent upon a glucocorticoid receptor (GR). Dexamethasone did not, however, induce mitophagy or alter the morphology of the mitochondrial network. In vivo, in neonatal mice, dexamethasone treatment induced cardiac expression of fatty acid oxidation genes. However, dexamethasone treatment of pregnant C57Bl/6 mice at embryonic day (E)13.5 or E16.5 failed to induce fatty acid oxidation genes in fetal hearts assessed 24 h later. Instead, at E17.5, fatty acid oxidation genes were downregulated by dexamethasone, as was GR itself. PGC-1α, required for glucocorticoid-induced maturation of primary mouse fetal cardiomyocytes in vitro, was also downregulated in fetal hearts at E17.5, 24 h after dexamethasone administration. Similarly, following a course of antenatal corticosteroids in a translational sheep model of preterm birth, both GR and PGC-1α were downregulated in heart. These data suggest that endogenous glucocorticoids support the perinatal switch to fatty acid oxidation in cardiomyocytes through changes in gene expression rather than gross changes in mitochondrial volume or mitochondrial turnover. Moreover, our data suggest that treatment with exogenous glucocorticoids may interfere with normal fetal heart maturation, possibly by downregulating GR. This has implications for clinical use of antenatal corticosteroids when preterm birth is considered a possibility. Key points: Glucocorticoids are steroid hormones that play a vital role in late pregnancy in maturing fetal organs, including the heart. In fetal cardiomyocytes in culture, glucocorticoids ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | unknown |
| Relation: | https://strathprints.strath.ac.uk/78198/1/Ivy_etal_JP_2021_Glucocorticoids_regulate_mitochondrial_fatty_acid_oxidation.pdf; Ivy, Jessica R. and Carter, Roderic N. and Zhao, Jin-Feng and Buckley, Charlotte and Urquijo, Helena and Rog-Zielinska, Eva A. and Panting, Emma and Hrabalkova, Lenka and Nicholson, Cara and Agnew, Emma J. and Kemp, Matthew W. and Morton, Nicholson N and Stock, Sarah J. and Wyrwoll, Caitlin and Ganley, Ian G. and Chapman, Karen E. (2021 ) Glucocorticoids regulate mitochondrial fatty acid oxidation in fetal cardiomyocytes. The Journal of Physiology , 599 (21). pp. 4901-4924. ISSN 1469-7793 |
| DOI: | 10.1113/JP281860 |
| الاتاحة: | https://strathprints.strath.ac.uk/78198/ https://strathprints.strath.ac.uk/78198/1/Ivy_etal_JP_2021_Glucocorticoids_regulate_mitochondrial_fatty_acid_oxidation.pdf https://doi.org/10.1113/JP281860 |
| Rights: | cc_by |
| رقم الانضمام: | edsbas.61CBC3B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1113/JP281860 |
|---|