Pallud S, Lennon A M, Ramauge M, Gavaret J M, Croteau W, Pierre M, Courtin F, St Germain D L
U96 INSERM-Unité de Recherche sur la Glande Thyroïde et la Regulation Hormonale, 80, rue du Général Leclerc, 94276 Le Kremlin-Bicêtre Cedex, France.
J Biol Chem. 1997 Jul 18;272(29):18104-10. doi: 10.1074/jbc.272.29.18104.
The iodothyronine deiodinases are a family of selenoproteins that metabolize thyroxine and other thyroid hormones to active and inactive metabolites in a number of tissues including brain. Using primary cultures of rat astroglial cells as a model system, we demonstrate that the mRNA for the type II iodothyronine deiodinase (DII) selenoenzyme is rapidly and markedly induced by forskolin and 8-bromo-cAMP. The induction of DII activity, however, was significantly impaired by culturing cells in selenium-deficient medium for 7 days. Under such conditions, the addition of selenium resulted in a rapid increase in cAMP-induced DII activity that was dose-dependent, with maximal effects noted within 2 h. Cycloheximide blocked this effect of selenium on restoring cAMP-induced DII activity, whereas actinomycin D did not. These data demonstrate that the DII selenoenzyme is expressed in cultured astrocytes and that the induction of DII activity by cAMP analogues appears to be mediated, at least in part, by pretranslational mechanisms. Furthermore, selenium deprivation impairs the expression of DII activity at the level of translation.
碘甲状腺原氨酸脱碘酶是一类硒蛋白家族,可在包括脑在内的多种组织中将甲状腺素及其他甲状腺激素代谢为活性和非活性代谢产物。以大鼠星形胶质细胞原代培养物作为模型系统,我们证明,II型碘甲状腺原氨酸脱碘酶(DII)硒酶的mRNA可被福斯可林和8-溴-环磷腺苷迅速且显著地诱导。然而,通过在缺硒培养基中培养细胞7天,DII活性的诱导受到显著损害。在这种条件下,添加硒会导致环磷腺苷诱导的DII活性迅速增加,且呈剂量依赖性,在2小时内达到最大效应。放线菌酮可阻断硒对恢复环磷腺苷诱导的DII活性的这种作用,而放线菌素D则不能。这些数据表明,DII硒酶在培养的星形胶质细胞中表达,并且环磷腺苷类似物对DII活性的诱导似乎至少部分是由翻译前机制介导的。此外,硒缺乏会在翻译水平上损害DII活性的表达。