Glucose and thyroid hormone co-regulate the expression of the intestinal fructose transporter GLUT5.
Glucose and thyroid hormone co-regulate the expression of the intestinal fructose transporter GLUT5.
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葡萄糖和甲状腺激素共同调节肠道果糖转运蛋白 GLUT5 的表达。
DOI：
10.1042/bj3390233
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
E. Brot
中科院分区：
文献类型：
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作者：
Miriam Matosin;José E. Mesonero;Thibaut J. Laroche;Michel Lacasa;Michel Lacasa;E. Brot
果糖转运蛋白GLUT5在Caco-2细胞中的表达受培养液[Mesonero，Matosin，Cambier，Rodriguez-Yoldi和Brot-Laroche(1995)Biochem]的碳水化合物含量控制。J.312,757-762]和细胞的代谢状态[Mahraoui，Takeda，Mesonero，Chantret，Dussaulx，Bell，and Brot-Laroche(1994)Biochem]。J.301,169-175]。在这项研究中，我们发现，在完全分化的Caco-2/TC7细胞中，甲状腺激素和葡萄糖以剂量依赖的方式增加GLUT5mRNA的丰度。利用插入荧光素酶报告基因上游的GLUT5启动子片段稳定转化的Caco-2/TC7细胞，我们定位了与该基因有关的3，3‘，5-L三碘甲状腺原氨酸(T3)和/或葡萄糖敏感的序列。葡萄糖反应是由启动子的-272/+41片段决定的，但只有在-338/+41区域，荧光素酶报告基因的转录才受到T3的刺激。GLUT5基因-338~-272位70bp的片段能够赋予异源胸苷激酶启动子对T3/葡萄糖的反应性。电泳迁移率分析表明，甲状腺激素受体α和β在Caco-2/TC7细胞中表达。他们进一步表明，GLUT5启动子的-308/-290区域与甲状腺激素受体/维甲酸X受体异二聚体结合，而葡萄糖和/或T3对核蛋白复合体的结合产生有害影响。
Expression of the fructose transporter GLUT5 in Caco-2 cells is controlled by the carbohydrate content of the culture media [Mesonero, Matosin, Cambier, Rodriguez-Yoldi and Brot-Laroche (1995) Biochem. J. 312, 757-762] and by the metabolic status of the cells [Mahraoui, Takeda, Mesonero, Chantret, Dussaulx, Bell, and Brot-Laroche (1994) Biochem. J. 301, 169-175]. In this study we show that, in fully differentiated Caco-2/TC7 cells, thyroid hormone and glucose increase GLUT5 mRNA abundance in a dose-dependent manner. Using Caco-2/TC7 cells stably transformed with various fragments of the GLUT5 promoter inserted upstream of the luciferase reporter gene, we localized the sequences that confer 3,3',5-l-tri-iodothyronine (T3)- and/or glucose-sensitivity to the gene. Glucose responsiveness is conferred by the -272/+41 fragment of the promoter, but it is only with the -338/+41 region that transcription of the luciferase reporter gene is stimulated by T3. This 70 bp fragment from position -338 to -272 of the GLUT5 gene is able to confer T3/glucose-responsiveness to the heterologous thymidine kinase promoter. Electrophoretic-mobility-shift assays demonstrate that thyroid hormone receptors alpha and beta are expressed in Caco-2/TC7 cells. They further show that the -308/-290 region of the GLUT5 promoter binds thyroid hormone receptor/retinoid X receptor heterodimers, and that glucose and/or T3 exert a deleterious effect on the binding of the nuclear protein complex.