THYROID HORMONES-CELL INTERACTIONS

甲状腺激素与细胞的相互作用

• 批准号: 3855376
• 负责人: J ROBBINS
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855376
• 关键词: affinity labeling; antihypercholesterolemic agent; brain cell; cell type; hepatocellular carcinoma; hormone regulation /control mechanism; intracellular transport; laboratory mouse; liver cells; membrane permeability; myoblasts; neoplastic cell culture for noncancer research; neuroblastoma; protein transport; stereochemistry; thyroid hormone binding protein; thyroxine; tissue /cell culture; transport proteins; triiodothyronine

Thyroid hormones must cross the plasma membrane to interact with nuclear or other intracellular receptors. While a saturable transport system for triiodo-thyronine (T3) has been demonstrated in many types of cells, this is less well established for thyroxine (T4). In mouse neuroblastoma cells, we found that T4 was actively and stereospecifically transported. Furthermore, L-system neutral amino acids were shown to be competitive inhibitors of both T3 and T4 transport. The inhibitory effect of phenylalanine may be of physiological importance. The binding of thyroid hormones to isolated neuroblast plasma membranes was studied by affinity labeling with bromoacetyl T3 and T4. There was selective binding of bromoacetyl T3 to a 27 kDa protein component, which may be involved in intracellular transport. 3,5-Dibromo-3'-pyridazinone-L-thyronine (L-94901), a novel thyromimetic drug, reduces hepatic cholesterol synthesis with little effect on cardiac function in rats. Kinetic analysis of T3 uptake in myoblasts, hepatoma cells and neuroblasts showed that L-94901 was a noncompetitive inhibitor of T3 uptake in all cell types, but Ki for liver and brain cells was 10-fold lower than for muscle derived cells. This differential effect on plasma membrane transport may explain the observations in the intact animal.

甲状腺激素必须穿过质膜与细胞核相互作用， 其他细胞内受体。虽然一个可饱和的运输系统， 三碘甲状腺原氨酸（T3）已被证明在许多类型的细胞，这 对甲状腺素（T4）不太确定。在小鼠神经母细胞瘤细胞中， 我们发现T4被主动地立体特异性地转运。 此外，L-系统中性氨基酸显示出竞争性 T3和T4转运的抑制剂。的抑制作用 苯丙氨酸可能具有生理重要性。 甲状腺激素与分离的成神经细胞质膜的结合是 通过用溴乙酰基T3和T4进行亲和标记来研究。有 溴乙酰T3与27 kDa蛋白组分的选择性结合， 可能参与细胞内转运。 3，5-二溴-3'-哒嗪酮-L-甲状腺原氨酸（L-94901） 药物，减少肝脏胆固醇合成，对心脏影响不大 在老鼠身上的功能成肌细胞、肝癌细胞T3摄取的动力学分析 细胞和神经母细胞表明，L-94901是一种非竞争性抑制剂， 所有细胞类型中的T3摄取，但肝和脑细胞的Ki为10倍 低于肌肉来源的细胞。这种对血浆的差异效应 膜转运可以解释在完整动物中的观察结果。