| Autor: |
Torres-Velarde JM; Department of Integrative Biology, University of California, Berkeley, California., Kolora SRR; Department of Integrative Biology, University of California, Berkeley, California., Khudyakov JI; Department of Biological Sciences, University of the Pacific, Stockton, California., Crocker DE; Department of Biology, Sonoma State University, Rohnert Park, California., Sudmant PH; Department of Integrative Biology, University of California, Berkeley, California., Vázquez-Medina JP; Department of Integrative Biology, University of California, Berkeley, California. |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2021 Sep 01; Vol. 321 (3), pp. R413-R428. Date of Electronic Publication: 2021 Jul 14. |
| DOI: |
10.1152/ajpregu.00052.2021 |
| Abstrakt: |
Elephant seals experience natural periods of prolonged food deprivation while breeding, molting, and undergoing postnatal development. Prolonged food deprivation in elephant seals increases circulating glucocorticoids without inducing muscle atrophy, but the cellular mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, and morphological analyses to study how seal cells adapt to sustained glucocorticoid exposure. Seal muscle progenitor cells differentiate into contractile myotubes with a distinctive morphology, gene expression profile, and metabolic phenotype. Exposure to dexamethasone at three ascending concentrations for 48 h modulated the expression of six clusters of genes related to structural constituents of muscle and pathways associated with energy metabolism and cell survival. Knockdown of the glucocorticoid receptor (GR) and downstream expression analyses corroborated that GR mediates the observed effects. Dexamethasone also decreased cellular respiration, shifted the metabolic phenotype toward glycolysis, and induced mitochondrial fission and dissociation of mitochondria-endoplasmic reticulum (ER) interactions without decreasing cell viability. Knockdown of DNA damage-inducible transcript 4 (DDIT4), a GR target involved in the dissociation of mitochondria-ER membranes, recovered respiration and modulated antioxidant gene expression in myotubes treated with dexamethasone. These results show that adaptation to sustained glucocorticoid exposure in elephant seal myotubes involves a metabolic shift toward glycolysis, which is supported by alterations in mitochondrial morphology and a reduction in mitochondria-ER interactions, resulting in decreased respiration without compromising cell survival. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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