Molecular and Physiological Characterization of Thyroid Hormone Transporter

甲状腺激素转运蛋白的分子和生理学特征

• 批准号: 10670111
• 负责人: ABE Takaaki
• 金额: $ 2.05万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670111/
• 关键词: transporter; Thyroid Hormone; Neuron; Bile Acid; Prostaglandin; Steroid Hormone; ステロイドホルモン

We have isolated a novel liver-specific organic anion transporter, LST-1, that is expressed exclusively in the human, rat and mouse liver. LST-1 is a new gene family located between the organic anion transporter family and prostaglandin transporter. LST-1 transport taurocholate (Km ; 13.6 μM) in a sodium-independent manner. LST-1 also shows broad substrate specificity. It transports conjugated steroids (dehydroepiandrosterone sulfate, estradiol-17β-glucuronide and estrone-3-sulfate), eicosanoids (prostaglandin EィイD22ィエD2, thromboxane BィイD22ィエD2, leukotriene CィイD24ィエD2, leukotriene EィイD24ィエD2), and thyroid hormones, reflecting hepatic multispecificity. LST-1 is probably the most important transporter in the human liver for clearance of bile acids and organic anions since hepatic levels of another organic anion transporter, OATP is very low. We have also isolated rat counter part, rlst-1. Rlst-1 is excusively expressed in the liver and in both the bile duct ligation model and the cecum ligation and puncture model, the mRNA expression levels of rlst-1 were down-regulate, suggesting rlst-1 may be under feedback regulation of cholestasis by biliary obstruction and/or sepsis.

我们分离出一种新型肝脏特异性有机阴离子转运蛋白 LST-1，它仅在人类、大鼠和小鼠肝脏中表达，LST-1 是位于有机阴离子转运蛋白家族和前列腺素转运蛋白 1 转运蛋白之间的新基因家族。牛磺胆酸盐（Km；13.6 μM）以不依赖钠的方式也表现出广泛的底物特异性。硫酸盐、雌二醇-17β-葡萄糖醛酸和雌酮-3-硫酸盐）、类二十烷酸（前列腺素 E-D22-D2、血栓素 B-D22-D2、白三烯 C-D24-D2、白三烯 E-D24-D2 D2）和甲状腺激素，反映肝脏的多特异性。 Rlst-1 可能是人类肝脏中清除胆汁酸和有机阴离子的最重要的转运蛋白，因为另一种有机阴离子转运蛋白 OATP 的肝脏水平非常低，我们还分离出了大鼠对应物 Rlst-1。在肝脏、胆管结扎模型和盲肠结扎穿刺模型中，rlst-1 mRNA 表达水平下调，提示 rlst-1 可能处于低水平。胆道梗阻和/或脓毒症对胆汁淤积的反馈调节。

项目成果

Kakyo M. et al.: "Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurochorate"Gastroenterology. 117. 770-775 (1999)

Kakyo M. 等人：“运输甲状腺激素和牛磺胆酸盐的新型有机阴离子转运蛋白亚型 (oatp3) 的分子特征和组织分布”胃肠病学。

Kakyo M.et al.: "Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurocholate"FEBS Lett.. 445. 343-346 (1999)

Kakyo M.等人：“运输甲状腺激素和牛磺胆酸盐的新型有机阴离子转运蛋白亚型 (oatp3) 的分子特征和组织分布”FEBS Lett.. 445. 343-346 (1999)

Tokui T. et al.: "Pravastatin,an HMG-CoA reductase inhibitor,is transported by rat liver organic anion transporting polypeptide,oatp2." Phamaceutical Res.(in press).

Tokui T. 等人：“普伐他汀是一种 HMG-CoA 还原酶抑制剂，由大鼠肝脏有机阴离子转运多肽 oatp2 转运。”

Kakyo M., Sakagami H., Nishio T., Nakai D., Nakagomi R., Tokui T., Naitoh T., Matsuno S., Kondo H., Abe T., and Yawo H.: "Immunohistochemical distribution and functional characterization of an organic anion transporting polypeptide2 (oatp2)"FEBS Lett.. 44

Kakyo M.、Sakagami H.、Nishio T.、Nakai D.、Nakagomi R.、Tokui T.、Naitoh T.、Matsuno S.、Kondo H.、Abe T. 和 Yawo H.：“免疫组织化学分布和功能

Abe T.et al.: "Molecular characterization and tissue distribution of a new organic anion transporter subtype (oatp3) that transport thyroid hormones and taurocholate"J. Biol. Chem.. 273. 22395-22401 (1998)

Abe T.等人：“运输甲状腺激素和牛磺胆酸盐的新型有机阴离子转运蛋白亚型 (oatp3) 的分子特征和组织分布”J.