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谷胱甘肽是否调节细胞中的甲状腺素脱碘酶活性?

Does glutathione regulate thyroxine deiodinase activity in cells?

作者信息

Sato K, Robbins J

出版信息

Horm Metab Res Suppl. 1984;14:30-5.

PMID:6595189
Abstract

Since iodothyronine monodeiodinase require reduced sulfhydryl groups to be active, and since hepatic nonprotein sulfhydryls are low in states associated with decreased formation of T3 from T4, a regulatory role for glutathione (GSH) has been postulated in thyroid hormone deiodination. Studies with cultured rat hepatocytes showed that a 90% decrease of total GSH, achieved by culturing cells in Cys, Met-deficient medium, did not alter 5'- or 5-deiodinase activity. The glutathione disulfide (GSSG) fraction remained constant, however. When the GSSG: total GSH ratio was increased by culturing the cells in 0.5 mM diamide, butylhydroperoxide, or 10(-5) M vinblastine, 5'-deiodination was decreased. In fetal mouse liver explants, 5'-deiodination and total GSH were decreased but the GSSG ratio was normal and the deiodinase Vmax was decreased. It is concluded that monodeiodinase activity in hepatocytes is not regulated by the total GSH concentration but is inversely correlated with the ratio of GSSG to total GSH.

摘要

由于碘甲状腺原氨酸单脱碘酶需要还原型巯基才能发挥活性,并且由于在与从T4生成T3减少相关的状态下肝脏非蛋白巯基含量较低,因此有人推测谷胱甘肽(GSH)在甲状腺激素脱碘过程中具有调节作用。对培养的大鼠肝细胞的研究表明,通过在缺乏半胱氨酸、甲硫氨酸的培养基中培养细胞使总GSH降低90%,并不会改变5'-或5-脱碘酶的活性。然而,谷胱甘肽二硫化物(GSSG)部分保持恒定。当通过在0.5 mM二酰胺、叔丁基过氧化氢或10^(-5) M长春碱中培养细胞使GSSG:总GSH比率增加时,5'-脱碘作用降低。在胎鼠肝脏外植体中,5'-脱碘作用和总GSH降低,但GSSG比率正常且脱碘酶的最大反应速度降低。得出的结论是,肝细胞中的单脱碘酶活性不受总GSH浓度的调节,而是与GSSG与总GSH的比率呈负相关。

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引用本文的文献

1
NADPH-dependent generation of a cytosolic dithiol which activates hepatic iodothyronine 5'-deiodinase. Demonstration by alkylation with iodoacetamide.NADPH 依赖的胞质二硫醇生成,该二硫醇可激活肝脏碘甲状腺原氨酸 5'-脱碘酶。通过碘乙酰胺烷基化进行证明。
Biochem J. 1986 Dec 1;240(2):559-66. doi: 10.1042/bj2400559.
2
Properties of cytosolic components activating rat hepatic 5' [corrected]-deiodination in the presence of NADPH.在NADPH存在下激活大鼠肝脏5'-脱碘作用的胞质成分的特性。 (注:原文中“5' [corrected]”推测可能是表述有误,这里按“5'-”翻译)
Biochem J. 1986 Mar 1;234(2):391-8. doi: 10.1042/bj2340391.
3
Inhibition of hepatic deiodination of thyroxine is caused by selenium deficiency in rats.
大鼠体内硒缺乏会导致肝脏中甲状腺素脱碘作用受到抑制。
Biochem J. 1987 Dec 1;248(2):443-7. doi: 10.1042/bj2480443.