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23.03.2004 | 2:26 PM

Mice with Targeted Disruption of the Dio2 Gene Have Cold-Induced Overexpression of the Uncoupling Protein 1 Gene but Fail to Increase Brown Adipose Tissue Lipogenesis and Adaptive Thermogenesis.

The Dio2 gene encodes the type 2 deiodinase (D2) that activates thyroxine (T4) to 3,3 ,5-triiodothyronine (T3), the disruption of which (Dio2 / ) results in brown adipose tissue (BAT)-specific hypothyroidism in an oth- erwise euthyroid animal. In the present studies, cold exposure increased Dio2 / BAT sympathetic stimula- tion 10-fold (normal 4-fold); as a […]

01.12.2003 | 12:00 AM

Endoplasmic Reticulum-Associated Degradation of the Human Type 2 Iodothyronine Deiodinase (D2) is Mediated via an Association between Mammalian UBC7 and the Carboxyl Region of D2.

The type 2 iodothyronine selenodeiodinase (D2) is an endoplasmic reticulum (ER)-resident seleno- protein that activates T4 to T3, playing a critical role in thyroid homeostasis. D2 has an approximately 45-min half-life due to selective ubiquitin-mediated ER-associated degradation (ERAD), a process of particular interest because it is accelerated by ex- posure to D2 substrates, T4 or […]

20.10.2003 | 2:06 PM

Triplets! Unexpected Structural Similarity Among the Three Enzymes That Catalyze Initiation and Termination of Thyroid Hormone Effects.

The three iodothyronine deiodinases catalyze the initiation (D1, D2) and termination (D3) of thyroid hormone effects in vertebrates. A recently conceived 3-dimensional model predicts that these enzymes share a similar structural organization and belong to the thioredoxin (TRX) fold superfamily. Their active center is a selenocysteine-containing pocket defined by the β1-α1-β2 motifs of the TRX […]

29.07.2003 | 2:46 PM

Spared bone mass in rats treated with thyroid hormone receptor TR -selective compound GC-1.

Thyrotoxicosis is frequently associated with increased bone turn- over and decreased bone mass. To investigate the role of thyroid hormone receptor- (TR ) in mediating the osteopenic effects of triiodothyronine (T3), female adult rats were treated daily (64 days) with GC-1 (1.5 g/100 g body wt), a TR -selective thyromimetic compound. Bone mass was studied […]

07.07.2003 | 9:45 AM

The Iodothyronine Selenodeiodinases Are Thioredoxin-fold Family Proteins Containing a Glycoside Hydrolase Clan GH-A-like Structure.

The three iodothyronine selenodeiodinases catalyze the initiation and termination of thyroid hormone ef- fects in vertebrates. Structural analyses of these pro- teins have been hindered by their integral membrane nature and the inefficient eukaryotic-specific pathway for selenoprotein synthesis. Hydrophobic cluster analy- sis used in combination with Position-specific Iterated BLAST reveals that their extramembrane portion be- […]

22.04.2003 | 10:02 AM

Deubiquitination of type 2 iodothyronine deiodinase by von Hippel–Lindau protein– interacting deubiquitinating enzymes regulates thyroid hormone activation.

The type 2 iodothyronine deiodinase (D2) is an integral membrane ER-resident selenoenzyme that acti- vates the pro-hormone thyroxine (T4) and supplies most of the 3,5,3′-triiodothyronine (T3) that is essential for brain development. D2 is inactivated by selective conjugation to ubiquitin, a process accel- erated by T4 catalysis and essential for the maintenance of T3 homeostasis. […]

24.03.2003 | 10:17 AM

In Vivo Dimerization of Types 1, 2, and 3 Iodothyronine Selenodeiodinases.

The goal of the present investigation was to test the hypoth- esis that types 1, 2, and 3 iodothyronine selenodeiodinases (D1, D2, and D3) can form homodimers. The strategy included transient coexpression of wild-type (wt) deiodinases (target), and FLAG-tagged alanine or cysteine mutants (bait) in human embryonic kidney epithelial cells. SDS-PAGE of the immuno- precipitation […]

31.01.2003 | 10:08 AM

Quantitation of Brown Adipose Tissue Perfusion in Transgenic Mice Using Near-Infrared Fluorescence Imaging.

Brown adipose tissue (BAT; brown fat) is the principal site of adaptive thermogenesis in the human newborn and other small mammals. Of paramount importance for thermogenesis is vascular perfusion, which controls the flow of cool blood in, and warmed blood out, of BAT. We have developed an optical method for the quantitative imaging of BAT […]

24.12.2002 | 11:17 AM

Neuropeptide Y1 and Y5 Receptors Mediate the Effects of Neuropeptide Y on the Hypothalamic- Pituitary-Thyroid Axis.

Neuropeptide Y (NPY) is one of the most important hypotha- lamic-derived neuropeptides mediating the effects of leptin on energy homeostasis. Central administration of NPY not only markedly stimulates food intake, but simultaneously in- hibits the hypothalamic-pituitary-thyroid axis (HPT axis), replicating the central hypothyroid state associated with fast- ing. To identify the specific NPY receptor subtypes […]

04.11.2002 | 10:25 AM

Human Type 3 Iodothyronine Selenodeiodinase Is Located in the Plasma Membrane and Undergoes Rapid Internalization to Endosomes.

The type 3 iodothyronine selenodeiodinase (D3) is an integral membrane protein that inactivates thyroid hor- mones. By using immunofluorescence cytochemistry confocal microscopy of live or fixed cells transiently expressing FLAG-tagged human D3 or monkey hepato- carcinoma cells expressing endogenous D3, we identi- fied D3 in the plasma membrane. It co-localizes with Na,K-ATPase , with the […]