Expression Patterns of WSB-1 and USP-33 Underlie Cell-Specific Posttranslational Control of Type 2 Deiodinase in the Rat Brain

• DOI: 10.1210/en.2007-0448
• Publication Date: 2007-07-13T01:07:40Z
• Authors: Csaba Fekete; Beatriz C. G. Fre...; Anikó Zeöld; Gábor Wittmann; Andrea Kádár; Zsolt Liposits; Marcelo A. Christ...; Praful Singru; Ronald M. Lechan; Antonio C. Bianco; Balázs Gereben
• Keywords: Male; Neurons; 0301 basic medicine; Intracellular Signaling Peptides and Proteins; Brain; Hyperthyroidism; Immunohistochemistry; Iodide Peroxidase; Polymerase Chain Reaction; Rats; Mice; 03 medical and health sciences; Hypothyroidism; Computer Systems; Astrocytes; Endopeptidases; Glial Fibrillary Acidic Protein; Animals; RNA, Messenger; Carrier Proteins; Protein Processing, Post-Translational; In Situ Hybridization

The type 2 deiodinase (D2) activates thyroid hormone and constitutes an important source of 3,5,3',-triiodothyronine in the brain. D2 is inactivated via WSB-1 mediated ubiquitination but can be rescued from proteasomal degradation by USP-33 deubiquitination. Using silico analysis published array data, we found a significant positive correlation between relative mRNA expression levels set 56 mouse tissues (r = 0.08; P < 0.04). Subsequently, used situ hybridization combined with immunocytochemistry rat brain to show that addition neurons, are differently expressed astrocytes tanycytes, two main expressing cell types this tissue. Tanycytes, which thought participate feedback regulation TRH neurons express both USP-33, indicating potential for deubiquitination these cells. Notably, only glial fibrillary acidic protein-positive throughout Although developmental environmental signals known regulate other tissues, our real-time PCR studies indicate changes status do not affect genes several regions, whereas mediobasal hypothalamus, gene were minimal. In conclusion, numerous suggests ubiquitin-related enzymes share additional substrates besides D2. Furthermore, data part homeostatic response hypothyroidism or hyperthyroidism.