STIMULATION OF EARLY GENE-EXPRESSION BY ANGIOTENSIN-II IN BOVINE ADRENAL GLOMERULOSA CELLS - ROLES OF CALCIUM AND PROTEIN-KINASE-C
STIMULATION OF EARLY GENE-EXPRESSION BY ANGIOTENSIN-II IN BOVINE ADRENAL GLOMERULOSA CELLS - ROLES OF CALCIUM AND PROTEIN-KINASE-C
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DOI：
10.1210/me.6.11.1889
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发表时间：
1992-11-01
影响因子：
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通讯作者：
CATT, KJ
中科院分区：
文献类型：
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作者：
CLARK, AJL;BALLA, T;CATT, KJ
肾上腺肾小球细胞是血管紧张素II （AII）的主要作用部位，它与AT1受体结合，刺激磷酸肌苷水解和Ca2+动员，并随后产生醛固酮。AII还影响肾上腺的生长和增殖，并促进胸腺嘧啶在肾上腺皮质细胞中的掺入。在原代培养的牛肾小球细胞中，发现AII可以诱导几种早期生长反应基因（c-fos、c-jun、JunB和krox24）的表达。AII的这种作用是剂量依赖性的，并被[Sar1，Ile8] AII和非肽拮抗剂DuP 753阻断，表明它是由AII受体的AT1亚型介导的。ACTH升高肾小球细胞中的cAMP，是c-fos表达的相对弱诱导剂，但在刺激JunB表达方面与AII一样有效。ACTH未进一步增强AII对c-fos表达的最大影响。Ca2+离子载体离子霉素诱导c-fos表达的能力表明，aii诱导细胞质Ca2+增加在产生c-fos反应中的作用。然而，Ca2+ atp酶抑制剂thapsigargin对细胞内Ca2+的动员，以及钾去极化对Ca2+内流的刺激，对c-fos表达的刺激作用较小。细胞外介质中Ca2+的遗漏，消除了aii诱导的Ca2+信号的平台期，而不影响Ca2+动员引起的早期增加，增强了aii诱导的c-fos反应的早期阶段，表明Ca2+对早期基因反应也有抑制作用。12-肉豆蔻酸酯（PMA）对蛋白激酶C的激活也刺激了C -fos的表达，但PMA和离子霉素联合使用并没有进一步提高C -fos的反应。staurosporine对蛋白激酶C的抑制，或由于长期暴露于PMA而使其耗竭，阻止了C -fos对PMA的反应，但仅部分抑制了对AII的反应，这表明AT1受体的刺激-转录偶联涉及其他因素。
The adrenal glomerulosa cell is a major site of action of angiotensin II (AII), which binds to AT1 receptors to stimulate phosphoinositide hydrolysis and Ca2+ mobilization, and the subsequent production of aldosterone. AII also influences adrenal growth and proliferation and promotes thymidine incorporation in adrenocortical cells. In primary cultures of bovine glomerulosa cells, AII was found to induce the expression of several early growth response genes (c-fos, c-jun, JunB, and Krox 24). This effect of AII was dose-dependent and was blocked by [Sar1,Ile8] AII and the nonpeptide antagonist DuP 753, indicating that it is mediated by the AT1 subtype of the AII receptor. ACTH, which elevates cAMP in glomerulosa cells, was a relatively weak inducer of c-fos expression but was as potent as AII in stimulating the expression of JunB. ACTH did not further enhance the maximal effect of AII on c-fos expression. The role of the AII-induced cytoplasmic Ca2+ increase in generating the c-fos response was suggested by the ability of the Ca2+ ionophore ionomycin to induce c-fos expression. However, mobilization of intracellular Ca2+ by the Ca2+ ATPase inhibitor thapsigargin, as well as the stimulation of Ca2+ influx by depolarization with potassium, were less potent stimuli of c-fos expression. Omission of Ca2+ from the extracellular medium, which abolishes the plateau phase of the AII-induced Ca2+ signal without affecting the early increase due to Ca2+ mobilization, enhanced the early phase of the AII-induced c-fos response, indicating that Ca2+ also has an inhibitory effect on the early gene response. Activation of protein kinase C by phorbol 12-myristate, 13-acetate (PMA) also stimulated c-fos expression, but the combination of PMA and ionomycin did not further increase the c-fos response. Inhibition of protein kinase C by staurosporine, or its depletion by prolonged exposure to PMA, prevented the c-fos response to PMA but only partially inhibited the response to AII, suggesting the involvement of other factors in stimulus-transcription coupling from the AT1 receptor.