T3-mediated gene expression is independent of PGC-1α

Wulf, Anne; Harneit, Angelika; Weitzel, Joachim M.

doi:10.1016/j.mce.2007.02.008

Cited by 14 publications

(14 citation statements)

References 30 publications

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“…Although recent report indicates that thyroid hormone-mediated gene expression patterns are not completely depending on PGC-1 activation (Wulf et al, 2007), the above data support the idea that a thyroid hormone-mediated activation of PGC-1 might help this coactivator to exert its function in adaptation to endocrine signals. On the other hand, additional factors might contribute to PGC-1 activation in response to other signals, such as low environmental temperature.…”

Section: Discussionsupporting

confidence: 52%

Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals

Venditti

Bari

Stefano

et al. 2009

Molecular and Cellular Endocrinology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 AbstractWe studied liver oxidative capacity and O 2 consumption in hypothyroid rats treated for 10 days with T 4 , or T 3 , or treated for 10 days with T 3 and exposed to cold for the last two days. The metabolic response of homogenates and mitochondria indicated that all treatments increased the synthesis of respiratory chain components, whereas only the cold induced mitochondrial proliferation. Determination of mRNA and protein expression of transcription factor activators, such as NRF-1 and NRF-2, and coactivators, such as PGC-1, showed that mRNA levels, except PGC-1 ones, were not related to aerobic capacities. Conversely, a strong correlation was found was between cytochrome oxidase activity and PGC-1 or NRF-2 protein levels.Such a correlation was not found for NRF-1. Our results strongly support the view that in rat liver PGC-1 and NRFs are responsible for the iodothyronine-induced increases in respiratory chain components, whereas their role in cold-induced mitochondrial proliferation needs to be further on clarified.

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Section: Discussionsupporting

confidence: 52%

Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals

Venditti

Bari

Stefano

et al. 2009

Molecular and Cellular Endocrinology

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“…Since the overall structure of this DBD mutant remains unaffected (Shibusawa et al 2003a), it is likely that a suggested protein-protein interaction domain remains intact. As also suggested for different members of the nuclear receptor family, these proteins are targets of post-translational modifications, which facilitate their function within the transrepression mechanism (Moeller et al 2005, Hiroi et al 2006, Kenessey & Ojamaa 2006, Storey et al 2006, Wulf et al 2007. Further investigations should target these questions with special emphasis on the DBD of TR.…”

Section: Discussionmentioning

confidence: 93%

The role of thyroid hormone receptor DNA binding in negative thyroid hormone-mediated gene transcription

Wulf¹,

Wetzel²,

Kebenko³

et al. 2008

Journal of Molecular Endocrinology

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Thyroid hormone 3,3 0 ,5-tri-iodothyronine (T 3 ) regulates gene expression in a positive and negative manner. Here, we analyzed the regulation of a positively (mitochondrial glycerol-3-phosphate dehydrogenase) and negatively T 3 -regulated target gene (TSHa). Thyroid hormone receptor (TR) activates mGPDH but not TSH promoter fragments in a mammalian one-hybrid assay. Furthermore, we investigated functional consequences of targeting TR to DNA independent of its own DNA-binding domain (DBD). Using a chimeric fusion protein of the DBD of yeast transcription factor Gal4 with TR, we demonstrated a positive regulation of gene transcription in response to T 3 . T 3 -mediated activation of this chimeric protein is further increased after an introduction of point mutations within the DBD of TR. Moreover, we investigated the capacity of TR to negatively regulate gene transcription on a DNA-tethered cofactor platform. A direct binding of TR to DNA via its own DBD is dispensable in this assay. We investigated functional consequences of point mutations affecting different domains of TR. Our data indicate that the DBD of TR plays a key role in direct DNA binding on positively but not on negatively T 3 -regulated target genes. Nevertheless, the DBD is involved in mediating negative gene regulation independent of its capacity to bind DNA.

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“…This experiment showed that silencing PGC-1α abolished the ability of T3 to induce PDK4, CPT-1a, PEPCK and C/EBPβ gene expression indicating that PGC-1α is an important coactivator for the T3 induction of these genes in primary hepatocytes. This experiment contrasts with a recent study conducted by Wetizel's group, as they reported that silencing PGC-1α had no effect on the induction of gene expression by T3 in rat pituitary (GC) cells (Wulf et al, 2007). In contrast with our studies, they measured the T3 effect on two other genes, glycerol-3-phosphate dehydrogenase (GPDH) and adenine nucleotide translocater 2 (ANT2).…”

Section: The Role Of the Pgc-1α In The Induction Of The Pdk4 By Thyrocontrasting

confidence: 99%

Regulation of Pyruvate Dehydrogenase Kinase 4 by Thyroid Hormone / Role of Peroxisome Proliferator Activated Receptor Gamma Coactivator-1 alpha and Ccaat Enhancer Binding Protein

Attia¹

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Pyruvate dehydrogenase kinase 4 (PDK4) regulates pyruvate oxidation through the phosphorylation and inhibition of the pyruvate dehydrogenase complex (PDC). PDC catalyzes the conversion of pyruvate to acetyl‐CoA and is an important control point in glucose and pyruvate metabolism. PDK4 gene expression is stimulated by thyroid hormone (T3), glucocorticoids and long chain fatty acids. Here, we have identified two binding sites for the thyroid hormone receptor (TRß) in the promoter of the PDK4 gene. In addition, we have investigated the role of transcriptional coactivators and found that the peroxisome proliferator activated receptor gamma coactivator (PGC‐1α) enhances the T3 induction of PDK4. Addition of T3 to rat hepatocytes increased the abundance of the PGC‐1α and its association with the PDK4 promoter. Administration of T3 to hypothyroid rats increased PGC‐1α protein levels in the liver. In addition, we observed enhanced association of PGC‐1α not only with the PDK4 gene but also with phosphoenolpyruvate carboxykinase (PEPCK) and carnitine palmitoyltransferase 1a (CPT‐1a) genes. Knock‐down of PGC‐1α in rat hepatocytes reduced the T3 induction of PDK4, PEPCK and CPT‐1a genes. Our results indicate that T3 regulates PGC‐1α abundance and association with hepatic genes and in turn PGC‐1α is an important participant in the T3 induction of selected genes.

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T3-mediated gene expression is independent of PGC-1α

Cited by 14 publications

References 30 publications

Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals

Involvement of PGC-1, NRF-1, and NRF-2 in metabolic response by rat liver to hormonal and environmental signals

The role of thyroid hormone receptor DNA binding in negative thyroid hormone-mediated gene transcription

Regulation of Pyruvate Dehydrogenase Kinase 4 by Thyroid Hormone / Role of Peroxisome Proliferator Activated Receptor Gamma Coactivator-1 alpha and Ccaat Enhancer Binding Protein

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