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06.11.2013 | 10:14 PM
T4 restores myelination and clinical recovery after brain hemorrhage. PMID: 24174657
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Intraventricular hemorrhage (IVH) remains a major cause of white matter injury in preterm infants with no viable therapeutic strategy to restore myelination. Maturation of oligodendrocytes and myelination is influenced by thyroid hormone (TH) signaling, which is mediated by TH receptor α (TRα) and TRβ. In the brain, cellular levels of TH are regulated by deiodinases, […]

28.10.2013 | 11:19 PM
D2 is retrotranslocated to the cytoplasm and proteasomes via p97/Atx3 complex. PMID: 24196352
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The type II iodothyronine deiodinase (D2) is a type I endoplasmic-reticulum (ER)-resident thioredoxin fold-containing selenoprotein that activates thyroid hormone. D2 is inactivated by ERassociated ubiquitination and can be reactivated by two USP-class D2-interacting deubiquitinases (DUBs). Here, we used D2-expressing cell models to define that D2 ubiquitination (UbD2) occurs via K48-linked ubiquitin chains and that exposure […]

16.07.2013 | 10:00 AM
Cardiac expression of D2 decreases mortality caused by cardiotoxic drug. PMID: 23861374
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Altered glucose metabolism in heart is an important characteristic of cardiovascular and metabolic disease. Since thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in 3,5,3`-triiodothyronine (T3) using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the α-myosin heavy chain (MHC) promoter (MHC-D2). […]

01.04.2013 | 10:00 AM
Hypothalamus-pituitary axis is wired to defend serum T3. PMID: 23524969
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Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3′-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback […]

14.02.2013 | 10:00 AM
Dexamethasone reduces energy expenditure. PMID: 23408649
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Objective: To investigate how long-term treatment with dexamethasone affects energy expenditure and adiposity in mice and whether this is influenced by feeding on a high fat diet (HFD). Design and Methods: Mice were placed on a HFD for 2 weeks and started on dexamethasone at 5mg/kg every other day during the next 7 weeks. Results: […]

21.09.2012 | 10:00 AM
Major role played by β1-adrenergic receptor in BAT. PMID: 22728333
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Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and the adrenergic receptor signaling pathway. Knowing that a mouse with triple b-receptor knockout (KO) is cold intolerant and obese, we evaluated the independent role played by the b1 isoform in energy homeostasis. First, the 30 min i.v. infusion of norepinephrine (NE) […]

20.06.2012 | 10:00 AM
Neuronal hypoxia induces nuclear import of D3. PMID: 22723689
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D3 redirection and accumulation in the cell nucleus is part of the hypoxia-induced reduction in thyroid hormone signaling. Inactivation of thyroid hormone in the nucleus, physically closer to where thyroid hormone receptors (TRs) are located, constitutes an advantageous mechanism to dampen thyroid hormone signaling and reduce metabolism. Studies of directed D3 glycosylation indicated that D3 […]

18.06.2012 | 9:44 PM
Hypothalamic secretory systems are influenced by TH. PMID: 22719854
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Hypothalamic neurosecretory systems are fundamental regulatory circuits influenced by thyroid hormone. Monocarboxylate-transporter-8 (MCT8)-mediated uptake of thyroid hormone followed by type 3 deiodinase (D3)-catalyzed inactivation represent limiting regulatory factors of neuronal T3 availability. In the present study we addressed the localization and subcellular distribution of D3 and MCT8 in neurosecretory neurons and addressed D3 function in […]

26.05.2012 | 10:00 AM
Inactivation of Dio3 in the heart causes fibrosis and LVH. PMID: 22403173
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Cardiac injury induces myocardial expression of the thyroid hormone inactivating type 3 deiodinase (D3), which in turn dampens local thyroid hormone signaling. Here, we show that the D3 gene (Dio3) is a tissue-specific imprinted gene in the heart, and thus, heterozygous D3 knockout (HtzD3KO) mice constitute a model of cardiac D3 inactivation in an otherwise […]

25.12.2011 | 10:00 AM
ER stress decreases thyroid hormone activation. PMID: 22053000
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Cells respond rapidly to endoplasmic reticulum (ER) stress by blocking protein translation, increasing protein folding capacity, and accelerating degradation of unfolded proteins via ubiquitination and ER-associated degradation pathways. The ER resident type 2 deiodinase (D2) is normally ubiquitinated and degraded in the proteasome, a pathway that is accelerated by enzyme catalysis of T4 to T3. […]