A novel mechanism for the inhibition of type 2 iodothyronine deiodinase by tumor necrosis factor α: involvement of proteasomal degradation

Endocrine Journal

Katsuhiko Tsunekawa¹  Takayuki Ogiwara¹  Tadashi Morimura¹  Masatomo Mori²  Masami Murakami¹  Osamu Araki¹ 

[1] Department of Clinical Laboratory Medicine, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan;Department of Medicine and Molecular Sciences, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan

关键词: Nonthyroidal illness;    Type 2 iodothyronine deiodinase;    Tumor necrosis factor α;    Proteasome;   

DOI  :  10.1507/endocrj.EJ11-0144

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(49)Cited-By(1)Thyroxine (T4) needs to be converted to 3,5,3’-triiodothyronine (T3) by iodothyronine deiodinase to exert its biological activity.Recent studies revealed the presence of type 2 iodothyronine deiodinase (D2) in human thyroid tissue, human skeletal muscle and other tissues, suggesting that D2 is involved in maintaining plasma T3 level in human.Tumor necrosis factor α (TNFα) is an inflammatory cytokine of which production is elevated in patients with nonthyroidal illness.Although several lines of evidence suggest the causal role of TNFα in nonthyroidal illness, detailed nature of the effect of TNFα on D2 remains unclear.In the present study, we identified D2 activity and D2 mRNA in TCO-1 cells, which were derived from human anaplastic thyroid carcinoma, and studied the mechanisms involved in the regulation of D2 expression by TNFα.The characteristics of the deiodinating activity in TCO-1 cells were compatible with those of D2 and Northern analysis demonstrated that D2 mRNA was expressed in TCO-1cells.D2 activity and D2 mRNA expression were rapidly increased by dibutyryl cAMP ((Bu)2cAMP).TNFα showed an inhibitory effect on (Bu)2cAMP-stimulated D2 activity in spite of little effect on (Bu)2cAMP-stimulated D2 mRNA expression.MG132, a proteasome inhibitor abolished TNFα suppression of D2 activity whereas BAY11-7082 or 6-Amino-4-(4-phenoxyphenylethylamino) quinazoline, inhibitors of nuclear factor-κB (NF-κB) failed to attenuate the effect of TNFα on D2 activity. These data suggest that a posttranslational mechanism through proteasomal degradation but not NF-κB activation is involved in the suppression of D2 by TNFα.

【 授权许可】

Unknown