Thyroid hormone (T3) has a profound influence on normal development, differentiation and metabolism, processes which are known to be regulated by the transcriptional coactivator PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator-1alpha). Since T3 rapidly induces PGC-1alpha expression, we investigated whether reduced PGC-1alpha levels lead to alterations in T3-mediated gene expression patterns. Using RNA interference, we reduced PGC-1alpha mRNA to approximately 10% of its initial concentration in rat pituitary GC cells. Knock-down of PGC-1alpha is accompanied by diminished protein concentration and decreased expression level of PGC-1alpha target genes, among them key enzymes involved in gluconeogenesis, mitochondrial biogenesis and fatty acid oxidation. PGC-1alpha, PGC-1beta and NRF-1 mRNA molecules were rapidly degraded with a half-life time of approximately 90min, but this was independent of T3 stimulation. Expression of T3-target genes was not changed upon knock-down of PGC-1alpha. Our data indicate that complex T3-mediated gene expression patterns are maintained independently of PGC-1alpha activation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.mce.2007.02.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thyroxine (T3)-mediated regulation of early cardiac repair in a chemical-induced hypoxia/reoxygenation model of adult zebrafish (Danio rerio).
Wound Repair Regen
December 2024
Department of Zoology, Trivenidevi Bhalotia College, Raniganj, West Bengal, India.
Hypoxia-mediated cardiac tissue injury and its repair or regeneration are one of the major health management challenges globally. Unlike mammals, lower vertebrate species such as zebrafish (Danio rerio) represent a natural model to study cardiac injury, repair and regeneration. Thyroxine (T3) has been hypothesised to be one of the endocrine factors responsible for the evolutionary trade-off for acquiring endothermy and regenerative capability in higher vertebrates.
View Article and Find Full Text PDFNuclear receptor corepressor 1 levels differentially impact the intracellular dynamics of mutant thyroid hormone receptors associated with resistance to thyroid hormone syndrome.
Mol Cell Endocrinol
December 2024
Department of Biology, William & Mary, 540 Landrum Drive, Integrated Science Center 3030, Williamsburg, VA, 23185, USA. Electronic address:
Thyroid hormone receptor α1 (TRα1) undergoes nucleocytoplasmic shuttling and mediates gene expression in response to thyroid hormone (T3). In Resistance to Thyroid Hormone Syndrome α (RTHα), certain TRα1 mutants have higher affinity for nuclear corepressor 1 (NCoR1) and may form stable complexes that are not released in the presence of T3. Here, we examined whether NCoR1 modulates intranuclear mobility and nuclear retention of TRα1 or RTHα-associated mutants in transfected human cells, as a way of analyzing critical structural components of TRα1 and to further explore the correlation between mutations in TRα1 and aberrant intracellular trafficking.
View Article and Find Full Text PDFTriiodo-L-thyronine (T3) downregulates Npr1 gene (coding for natriuretic peptide receptor-A) transcription in H9c2 cells: involvement of β-AR-ROS signaling.
Endocrine
September 2024
Peptide Research and Molecular Cardiology Unit, Department of Biochemistry, University of Madras, Guindy campus, Chennai, Tamil Nadu, 600025, India.
Introduction: Natriuretic peptide receptor-A (NPR-A) signaling system is considered as an intrinsic productive mechanism of the heart that opposes abnormal cardiac remodeling and hypertrophic growth. NPR-A is coded by Npr1 gene, and its expression is downregulated in the hypertrophied heart.
Aim: We sought to examine the levels of Npr1 gene transcription in triiodo-L-thyronine (T3) treated hypertrophied cardiomyocyte (H9c2) cells, in vitro, and also the involvement of β-adrenergic receptor (β-AR) - Reactive oxygen species (ROS) signaling system in the down-regulation of Npr1 transcription also studied.
Synthetic Thyroid Hormone Receptor-β Agonists Promote Oligodendrocyte Precursor Cell Differentiation in the Presence of Inflammatory Challenges.
Pharmaceuticals (Basel)
August 2023
Department of Pharmacy and Biotechnology (FaBit), University of Bologna, 40126 Bologna, Italy.
Oligodendrocytes and their precursors are the cells responsible for developmental myelination and myelin repair during adulthood. Their differentiation and maturation processes are regulated by a complex molecular machinery driven mainly by triiodothyronine (T3), the genomic active form of thyroid hormone, which binds to thyroid hormone receptors (TRs), regulating the expression of target genes. Different molecular tools have been developed to mimic T3 action in an attempt to overcome the myelin repair deficit that underlies various central nervous system pathologies.
View Article and Find Full Text PDFRole of aerobic exercise in ameliorating NASH: Insights into the hepatic thyroid hormone signaling and circulating thyroid hormones.
Front Endocrinol (Lausanne)
January 2023
Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
Aim: Triiodothyronine (T3) administration significantly eliminates hepatic steatosis and also has a therapeutic effect on non-alcoholic steatohepatitis (NASH). However, the potential mechanism by which T3-mediated exercise improves NASH is unknow. This study aimed to explore the effect of aerobic exercise on liver injury in NASH.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!