Expression patterns of WSB-1 and USP-33 underlie cell-specific posttranslational control of type 2 deiodinase in the rat brain

Csaba Fekete, Beatriz C G Freitas, A. Zeöld, Gábor Wittmann, Andrea Kádár, Z. Liposits, Marcelo A. Christoffolete, Praful Singru, Ronald M. Lechan, Antonio C. Bianco, B. Gereben

Research output: Contribution to journalArticle

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Abstract

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

Original languageEnglish
Pages (from-to)4865-4874
Number of pages10
JournalEndocrinology
Volume148
Issue number10
DOIs
Publication statusPublished - Oct 2007

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Iodide Peroxidase
Brain
Ependymoglial Cells
Ubiquitination
Astrocytes
Gene Expression
Neurons
Messenger RNA
Glial Fibrillary Acidic Protein
Triiodothyronine
Hyperthyroidism
Ubiquitin
Hypothyroidism
Thyroid Hormones
Computer Simulation
Hypothalamus
In Situ Hybridization
Real-Time Polymerase Chain Reaction
Thyroid Gland
Immunohistochemistry

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Expression patterns of WSB-1 and USP-33 underlie cell-specific posttranslational control of type 2 deiodinase in the rat brain. / Fekete, Csaba; Freitas, Beatriz C G; Zeöld, A.; Wittmann, Gábor; Kádár, Andrea; Liposits, Z.; Christoffolete, Marcelo A.; Singru, Praful; Lechan, Ronald M.; Bianco, Antonio C.; Gereben, B.

In: Endocrinology, Vol. 148, No. 10, 10.2007, p. 4865-4874.

Research output: Contribution to journalArticle

Fekete, C, Freitas, BCG, Zeöld, A, Wittmann, G, Kádár, A, Liposits, Z, Christoffolete, MA, Singru, P, Lechan, RM, Bianco, AC & Gereben, B 2007, 'Expression patterns of WSB-1 and USP-33 underlie cell-specific posttranslational control of type 2 deiodinase in the rat brain', Endocrinology, vol. 148, no. 10, pp. 4865-4874. https://doi.org/10.1210/en.2007-0448
Fekete, Csaba ; Freitas, Beatriz C G ; Zeöld, A. ; Wittmann, Gábor ; Kádár, Andrea ; Liposits, Z. ; Christoffolete, Marcelo A. ; Singru, Praful ; Lechan, Ronald M. ; Bianco, Antonio C. ; Gereben, B. / Expression patterns of WSB-1 and USP-33 underlie cell-specific posttranslational control of type 2 deiodinase in the rat brain. In: Endocrinology. 2007 ; Vol. 148, No. 10. pp. 4865-4874.
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abstract = "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 mediated deubiquitination. Using an in silico analysis of published array data, we found a significant positive correlation between the relative mRNA expression levels of WSB-1 and USP-33 in a set of 56 mouse tissues (r = 0.08; P <0.04). Subsequently, we used in situ hybridization combined with immunocytochemistry in rat brain to show that in addition to neurons, WSB-1 and USP-33 are differently expressed in astrocytes and tanycytes, the two main D2 expressing cell types in this tissue. Tanycytes, which are thought to participate in the feedback regulation of TRH neurons express both WSB-1 and USP-33, indicating the potential for D2 ubiquitination and deubiquitination in these cells. Notably, only WSB-1 is expressed in glial fibrillary acidic protein-positive astrocytes throughout the brain. Although developmental and environmental signals are known to regulate the expression of WSB-1 and USP-33 in other tissues, our real-time PCR studies indicate that changes in thyroid status do not affect the expression of these genes in several rat brain regions, whereas in the mediobasal hypothalamus, changes in gene expression were minimal. In conclusion, the correlation between the relative mRNA levels of WSB-1 and USP-33 in numerous tissues that do not express D2 suggests that these ubiquitin-related enzymes share additional substrates besides D2. Furthermore, the data indicate that changes in WSB-1 and USP-33 expression are not part of the brain homeostatic response to hypothyroidism or hyperthyroidism.",
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