Coordinated regulation of mitochondrial turnover by estrogen related receptor alpha and and thyroid hormone
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE81132 | GEO | 2017/03/01
SECONDARY ACCESSION(S): PRJNA320690
REPOSITORIES: GEO
Similar Datasets
Project description:Following exposure to chemoradiation, EAC cells increase their mitochondrial content and associated metabolic processes, which drives treatment resistance. Inhibition of this response using clinically applicable inhibitors of ESRRA in combination with (chemo)radiation shows promising anti-tumor activities and could be further developed for clinical use.
2022-10-17 | GSE184654 | GEO
Project description:Here, we treated a nove ER-positive PDX (UCD12) supplemented with estrogen (E2) with or without thyroid hormone (TH) and/or tamoxifen (Tam). Each treatment cohort (E2 alone, E2 + TH, E2 + Tam, E2+ TH+Tam) tumor growth over time was monitored. Tumors treated with TH continued to grow more that E2 alone. Tamoxifen blocked E2-mediated tumor growth, however in the presence of TH this was not seen. This analysis identified thyroid hormone as a potential driver of tumor progression in the context of estrogen receptor positive PDX tumor model.
2020-05-14 | GSE131276 | GEO
Project description:1. The effect of thyroidectomy on turnover rates of liver, kidney and brain mitochondrial proteins was examined. 2. In the euthyroid state, liver and kidney mitochondria show a synchronous turnover with all protein components showing more or less identical half-lives compared with the whole mitochondria. The brain mitochondrial proteins show asynchronous turnover, the soluble proteins having shorter half-lives. 3. Mitochondrial DNA (m-DNA) of liver and kidney has half-lives comparable with that of whole mitochondria from these tissues. 4. Thyroidectomy results in increased half-lives of liver and kidney mitochondria, with no apparent change in the half-life of brain mitochondria. 5. A detailed investigation of the turnover rates of several protein components revealed a significant decrease in the turnover rates of mitochondrial insoluble proteins from the three tissues under study. 6. The turnover rates of m-DNA of liver and kidney show a parallel decrease. 7. Thus it is apparent that thyroid hormone(s) may have a regulatory role in maintaining the synchrony of turnover of liver and kidney mitochondria in the euthyroid state. Turnover of brain mitochondria may perhaps be regulated by some other factor(s) in addition to thyroid hormone(s). 8. It seems likely that during mitochondrial turnover m-DNA and insoluble proteins may constitute a major unit. 9. The mitochondrial protein contents of the three tissues are not affected by thyroidectomy. 10. No correlation was seen between the turnover rate of mitochondria and cathepsin activity in any of the tissues under study in normal or thyroidectomized animals. 11. On the other hand, mitochondrial proteinase activity shows good correlation with the turnover rates of mitochondria in normal animals, and a parallel decrease in activity comparable with the decreased rates of turnover is observed after thyroidectomy. 12. It is concluded that mitochondrial proteinase activity may play a significant role in their protein turnover.
| S-EPMC1172481 | biostudies-other
Project description:The thyroid hormone (TH)-controlled recruitment process of brown adipose tissue (BAT) is not fully understood. Here, we show that long-term treatment of T3, the active form of TH, increases the recruitment of thermogenic capacity in interscapular BAT of male mice through hyperplasia by promoting the TH receptor α-mediated adipocyte progenitor cell proliferation. Our single-cell analysis reveals the heterogeneous nature and hierarchical trajectory within adipocyte progenitor cellsof interscapular BAT. Further analyses suggest that T3 facilitates cell state transition from a more stem-like state towards a more committed adipogenic state and promotes cell cycle progression towards a mitotic state in adipocyte progenitor cells, through mechanisms involving the action of Myc on glycolysis. Our findings elucidate the mechanisms underlying the TH action in adipocyte progenitors residing in BAT and provide a framework for better understanding of the TH effects on hyperplastic growth and adaptive thermogenesis in BAT depot at a single-cell level.
2022-05-13 | GSE186188 | GEO
Project description:Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor ? (ERR?), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERR? in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERR?, in both the LDHA and LDHB genes. The interaction between ERR? and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERR? expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERR? by a process distinct from that proposed by the recently revisited Warburg hypothesis.
| S-EPMC3596295 | biostudies-literature
Project description:Thyroid hormone (TH) and TH receptors (TRs) α and β act by binding to TH response elements (TREs) in regulatory regions of target genes. This nuclear signaling is established as the canonical pathway for TH action. In addition, however, TRs can activate intra-cellular second messenger signaling pathways. Whether such non-canonical TR signaling is physiologically relevant in vivo is unknown. Here we generated knock-in mice with a mutation in the TR DNA-binding domain that abrogates binding to DNA and TREs and leads to a complete loss of canonical TH action. We show that several important physiological TH effects are preserved despite disrupted DNA-binding, most notably heart rate, body temperature, blood glucose and triglyceride concentration, all of which were regulated by non-canonical TR signaling. Additionally, we confirm that TRE-binding defective TRβ leads to disruption of the hypothalamic-pituitary-thyroid axis with resistance to TH, while mutation of TRα causes a severe delay in skeletal development, showing TRE-mediated and tissue-specific canonical signaling. Our findings provide first in vivo evidence that non-canonical TR signaling exerts important cardiometabolic effects, which are clearly separated from canonical actions. Consequently, these data challenge the current paradigm that TH action is exclusively mediated through regulation of gene transcription at the nuclear level.
2017-11-01 | GSE104877 | GEO
Project description:Premetamorphic Xenopus laevis tadpoles brain ventricle cells respond to thyroid hormone by proliferation and subsequent differentiation. The goal of this experiment is to identify the genes involved in the TH-induced proliferation pathway in tadpole brain and compare it to TH-induced proliferation and differentiation program in tadpole limb. Xenopus tadpoles (NF54) were treated with 1 mM methimazole in 0.1 X MMR solution for 1 week to block the endogenous TH production and reduce the TH present in the system of the tadpole. They were then treated with 100 nM T3 in 1 mM methimazole and 0.1 x MMR for another 24h and 48h or without T3 for 48h (control group). Brains from the tadpoles were dissected at the end of the experiment. Keywords: development or differentiation design,organism part comparison design,reference design,replicate design,time series design
2005-10-04 | GSE3402 | GEO
Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression. Agilent two-color microarray were used to perform gene expression profile in euthyroid and hypothyroid male mouse livers, 5 biological replicates. TLDA (Taqman microRNA Array) was used to explore the miRNA expression profile in euthyroid and hypothyroid male mouse livers, 4 biological replicates.
2010-08-20 | E-GEOD-21277 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression.
2010-08-20 | GSE21277 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE16017: Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part B GSE16018: Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part C GSE16074: Thyroid Hormone (TH) Controls The Remodeling Of The Pancreas And The Liver, Part A Refer to individual Series
2010-05-16 | E-GEOD-16075 | biostudies-arrayexpress