The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel.
The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel.
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DOI：
10.1046/j.1523-1755.2000.00964.x
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发表时间：
2000-04
影响因子：
19.6
通讯作者：
A. Náray-Fejes-Tóth;G. Fejes-Tóth
中科院分区：
文献类型：
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作者：
A. Náray-Fejes-Tóth;G. Fejes-Tóth
SGK是醛固酮诱导的盐皮质激素靶细胞基因，调节上皮性钠通道。醛固酮增加紧致上皮细胞对钠的重吸收。这种刺激效应的早期阶段被认为涉及心尖钠通道的激活。为了识别启动这种效应的即刻早期基因，我们使用了基于聚合酶链式反应的消减杂交和差异显示技术的组合。这篇综述总结了我们最近的发现。在天然的盐皮质激素靶细胞中，即在皮质集合管细胞中，醛固酮迅速增加一种可能的丝氨酸/苏氨酸激酶，SGK(或血清和糖皮质激素调节的激酶)的mRNA水平。SGK基因的诱导在加入醛固酮后30分钟内发生，不需要从头合成蛋白质，表明SGK是一种即刻/早期的醛固酮诱导基因。醛固酮对SGK的诱导是通过盐皮质激素受体(MRS)介导的，因为它可以被MR拮抗剂ZK91857阻止，但不能被糖皮质激素拮抗剂RU486阻止。除醛固酮外，纯糖皮质激素受体激动剂RU28362还能诱导原代培养的兔CD细胞和M-1小鼠CD细胞系SGK mRNA的表达。SGK信使核糖核酸水平也受介质渗透压变化的影响。在M-1细胞中，细胞在轻度低渗液中孵育1小时可降低SGK基因的表达水平，而在高渗液中孵育1小时则产生相反的变化。为了确定SGK是否参与上皮性钠通道(ENaC)的调节，我们在非洲爪哇卵母细胞中与三个ENaC亚基共表达了SGK全长cRNA。SGK的表达导致对阿米洛利敏感的钠电流显著增加，提示该蛋白激酶在醛固酮刺激的钠转运的早期阶段起重要作用。这些结果表明，SGK在天然MR靶细胞中是一个由醛固酮诱导的即刻/早期基因，参与了离子转运和可能的细胞体积的调节。
The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel. Aldosterone increases sodium reabsorption in tight epithelia. The early phase of this stimulatory effect is thought to involve activation of apical sodium channels. To identify immediate-early genes that initiate this effect, we used a combination of polymerase chain reaction-based subtractive hybridization and differential display techniques. This review summarizes our recent findings. Aldosterone rapidly increases mRNA levels of a putative Ser/Thr kinase, sgk (or serum- and glucocorticoid-regulated kinase), in the native mineralocorticoid target cells, that is, in cortical collecting duct (CCD) cells. The induction of sgk mRNA occurs within 30 minutes of the addition of aldosterone and does not require de novo protein synthesis, indicating that sgk is an immediate/early aldosterone-induced gene. Induction of sgk by aldosterone is mediated through mineralocorticoid receptors (MRs), since it is prevented by ZK91857, an MR antagonist, but not by RU486, a glucocorticoid antagonist. In addition to aldosterone, RU28362, a pure glucocorticoid receptor agonist, also induced sgk mRNA, both in primary cultures of rabbit CCD cells and in the M-1 mouse CCD cell line. Sgk mRNA levels are also influenced by changes in the osmolality of the medium. In M-1 cells, incubation of cells for one hour in a mildly hypotonic medium decreased sgk mRNA levels, whereas incubation in hypertonic medium brought about opposite changes. To determine whether sgk is involved in the regulation of the epithelial sodium channel (ENaC), we coexpressed the full-length sgk cRNA in Xenopus oocytes with the three ENaC subunits. Expression of sgk resulted in a significant increase in the amiloride-sensitive Na current, suggesting that this protein kinase plays an important role in the early phase of aldosterone-stimulated Na transport. These results indicate that sgk is an aldosterone-induced immediate/early gene in native MR target cells, and is involved in the regulation of ion transport and possibly cell volume.