Transcriptional control of sodium transport in tight epithelia by adrenal steroids
Transcriptional control of sodium transport in tight epithelia by adrenal steroids
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DOI：
10.1007/bf00232796
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发表时间：
1995-03
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影响因子：
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通讯作者：
F. Verrey
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作者：
F. Verrey
结论图3A和图3B所示的肾上腺皮质激素对致密上皮细胞钠转运作用的模型分为两个阶段：早期阶段，预先存在的钠转运机制被激活，晚期阶段，机制的转运能力增加。基于诱导转运功能方面的差异、干扰转录调节的试剂的选择性作用以及晚期反应阶段与转运蛋白合成和表达增加的相关性，区分了这两个连续阶段[26，45，46，98，99，124]。这些观察结果表明，钠运输的双峰刺激可能涉及两个不同的基因网络，这是直接（在生理意义上）和独立的刺激的作用的受体复合物和以下的“分子”级联（seesection分子和生理级联）。在实验情况下发现的反应的相对明确的时间分离可能是两个网络的固有属性的结果。事实上，为了产生快速的功能变化，参与早期反应的基因必须编码在mRNA和蛋白质水平上具有相对短的半衰期的产物。相比之下，在肾上腺类固醇作用的晚期阶段增加的Na转运机制的组成元件具有相对长的半衰期，如Na，K-ATP酶[82]所示。因此，即使在转录的变化可能会发生在早期的激素治疗过程中，他们对蛋白质的合成和池的影响，只有缓慢，并经过一个相当长的滞后期。一方面，正在进行的研究将很快提供更多的信息肾上腺类固醇调节基因的性质，时间进程和激素/受体特异性。另一方面，新的技术和分子工具的可用性，以研究蛋白质的钠转运机制大大增加了研究其调节肾上腺类固醇的可能性。因此，这将是一个迷人的挑战，从这两种方法中出现的数据，似乎只有方法和工具的组合将允许逐步填补理解的差距，这仍然是转录效应和运输调节之间的差距。
ConclusionsThe model for the adrenal steroid action on Na transport in tight epithelia as depicted in Fig. 3AandBdissociates two phases: an early phase during which the pre-existing Na transport machinery is activated and a late phase during which the transport capacity of the machinery is increased. These two sequential phases have been distinguished based on differences in functional aspects of the induced transport, on selective effects of agents interfering with transcriptional regulation and on a correlation of the late response phase with an increase in transport protein synthesis and expression [26, 45, 46, 98, 99, 124]. These observations suggest that a bimodal stimulation of Na transport could involve two different gene networks which are directly (in the physiological meaning) and independently stimulated by the action of the hormone-receptor complex and the following “molecular” cascades (seesection Molecular and Physiological Cascades). The relatively clear temporal dissociation of the responses found in experimental situations is probably the consequence of inherent properties of the two networks. Indeed, to generate rapid functional changes, the genes involved in the early response must encode products which have relatively short half-lifes at the mRNA and protein levels. In contrast, the constitutive elements of the Na transport machinery that are increased during the late phase of adrenal steroid action have, as shown for the Na,K-ATPase [82], relatively long half-lifes. Consequently, even though changes in transcription may take place early in the course of the hormonal treatment, they impact on protein synthesis and pools only slowly and after a substantial lag period.On the one hand, ongoing research will soon provide more information on the nature, time course and hormone/receptor specificity of adrenal-steroid-regulated genes. On the other hand, the availability of new technical and molecular tools to study the proteins of the Na transport machinery greatly increases the possibilities for studying its regulation by adrenal steroids. Consequently, it will be a fascinating challenge to relate the data emerging from both approaches, and it appears that only a combination of methods and tools will allow to progressively fill the gap of understanding which still lies between the transcriptional effects and the transport regulation.