Coordinate regulation of rat liver genes by thyroid hormone and dietary carbohydrate.
Coordinate regulation of rat liver genes by thyroid hormone and dietary carbohydrate.
复制标题
甲状腺激素和膳食碳水化合物对大鼠肝脏基因的协调调节。
DOI：
10.1111/j.1749-6632.1986.tb15518.x
复制
发表时间：
1986
影响因子：
5.2
通讯作者：
Towle,HC
中科院分区：
文献类型：
--
作者：
Tao,TY;Towle,HC
许多基因产物在肝脏中的表达受到甲状腺激素和膳食碳水化合物的协调调节。例如，大鼠的肝脏苹果酸酶是通过注射3，5，3‘-三碘-~-甲状腺原氨酸(T_1)或喂饲高碳水化合物、脱脂(CHO)饲料来诱导的。V3对原代培养的大鼠肝细胞的研究表明，T_1和葡萄糖都可以在肝细胞水平上直接作用于刺激苹果酸酶的合成！通过无细胞翻译和双向凝胶电泳法对大约230种肝脏信使核糖核酸进行检测，发现T-和CHO-饮食反应结构域之间存在广泛程度的重叠。“因此，将大鼠从标准饮食转换为CHO-饮食会导致10种mRNA翻译产物的相对水平发生变化。除一个外，所有这些基因都对升高的血浆T3水平有反应，而且在每种情况下，变化的方向(即，阳性或阴性)是相同的。由于升高的T3和CHO饮食都会导致脂肪酸合成增加，所以这些mRNA产物的一部分，如苹果酸酶，可能参与了适应性高脂生成。这些产物提供了一个有趣的系统来研究激素和营养刺激对基因调控的协调。在过去的几年里，我们一直专注于其中一个肝脏基因产物的调控，指定为14点。14点最初是根据其翻译产物的性质确定的，它的M为17 00O，等电点约为4.9。6点14基因的表达由于其快速的诱导动力学而特别受关注。单次注射T_1后，甲状腺功能减退大鼠的Spot14基因表达水平增加，并在10~20分钟之间存在滞后时间。在原代培养的肝细胞中，在培养液中加入T_2可使Spot 14的mRNA水平升高。这种基因产物的快速反应表明，它可能是对激素或营养刺激的主要反应。
The expression of many gene products in the liver is coordinately regulated by thyroid hormones and dietary carbohydrate. For example, hepatic malic enzyme in the rat is induced by either injection of 3, 5, 3'-triiodo-~-thyronine (T,) or feeding of a high-carbohydrate, fat-free (CHO) diet.'The regulation by these two stimuli is exerted at a pretranslational level? v3 Studies on isolated primary rat hepatocytes in culture indicate that both T, and glucose can act directly at the hepatocellular level to stimulate malic enzyme synthesis! An examination of approximately 230 hepatic mRNA species by cell-free translation and two-dimensional gel electrophoresis has revealed an extensive degree of overlap between the T,-and CHO-diet-responsive domain^."^ Thus, switching rats from a standard chow diet to a CHO diet led to alterations in the relative levels of 10 mRNA translational products. All but one of these mRNA species also responded to elevated plasma T3 levels, and in each case the direction of change (that is, positive or negative) was the same. Because both elevated T3 and the CHO diet result in increased fatty acid synthesis, it is possible that a subset of these mRNA products, like malic enzyme, are involved in adaptive hyperlipogenesis. These products provide an interesting system to study coordinate gene regulation by hormonal and nutritional stimuli.In the past few years, we have focused on the regulation of one of these hepatic gene products, designated spot 14. Spot 14 was first identified by the nature of its translational product, which has an M, of 17 OOO and a PI of about 4.9. 6 The expression of the spot 14 gene was of particular interest due to its rapid kinetics of induction. Following a single injection of T, into hypothyroid rats, spot 14 mRNA levels increased with a lag time between 10 and 20 min.'A similar lag time was observed following the intragastric administration of sucrose to normal rats? In cultures of primary hepatocytes, spot 14 mRNA levels are increased by addition of T, to the media? The rapidity of the response of this gene product suggests that it may be responding as a primary event to the hormonal or nutritional stimuli.