• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >Sgk1-Dependent Stimulation of Cardiac Na+/H+ Exchanger Nhe1 by Dexamethasone
【24h】

Sgk1-Dependent Stimulation of Cardiac Na+/H+ Exchanger Nhe1 by Dexamethasone

机译：地塞米松对心脏Na + / H +交换子Nhe1的Sgk1依赖性刺激。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background/Aims: The serum- and glucocorticoid-inducible kinase Sgk1 contributes to cardiac remodeling and development of heart failure, which is paralelled by Sgk1-dependent stimulation of the cardiac Na+/H+ exchanger Nhe1. Glucocorticoids are powerful stimulators of Sgk1 expression and influence cardiac remodeling. The present study thus explored whether the glucocorticoid receptor agonist dexamethasone influenced cardiac Sgk1 expression, as well as activity, expression and phosphorylation at Ser703 of the cardiac Na+/H+ exchanger Nhe1. Methods: Experiments were performed in HL-1 cardiomyocytes and gene targeted mice lacking functional Sgk1 (sgk1-/-) and respective wild type mice (sgk1+/+). Gene expression was determined by quantitative RT-PCR and Nhe1 phosphorylation was determined utilizing a specific antibody against a 14-3-3 binding motif at P-Ser703, which represents a putative phosphorylation site recognition motif for Sgk1 and is involved in Nhe1 activation. Cytosolic pH (pHi) was determined utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence and Nhe activity by the Na+-dependent realkalinization after an ammonium pulse. Results: Treatment of HL-1 cardiomyocytes with dexamethasone was followed by a significant increase in Sgk1 mRNA expression, parallelled by increased Na+/H+ exchanger activity. Furthermore, dexamethasone significantly increased Nhe1 and Spp1 mRNA expression. The effects of dexamethasone were blunted by cotreatment of HL-1 cardiomyocytes with the Sgk1 inhibitor EMD638683. Cotreatment with Nhe1 inhibitor cariporide similarly prevented dexamethasone-stimulated Spp1 mRNA expression. In sgk1+/+ mice, dexamethasone significantly increased cardiac Sgk1 mRNA levels. In sgk1+/+ mice, but not in sgk1-/- mice, dexamethasone significantly increased cardiac Nhe1 mRNA expression and Nhe1 phosphorylation at Ser703. Furthermore, cardiac Spp1, Ctgf, Nppa and Nppb mRNA levels were significantly increased in dexamethasone treated sgk1+/+ mice, effects significantly blunted in sgk1-/- mice. Conclusions: Sgk1 is critically involved in the phosphorylation and activation of the cardiac Na+/H+ exchanger Nhe1.
机译：背景/目的：血清和糖皮质激素诱导的激酶Sgk1有助于心脏重构和心力衰竭的发展，这与心脏Na + / H + < / sup>交换器Nhe1。糖皮质激素是Sgk1表达的强大刺激剂，并影响心脏重构。因此，本研究探讨了糖皮质激素受体激动剂地塞米松是否影响心脏Sgk1的表达，以及心脏Na + / H 的活性，表达和磷酸化。 > + 交换器Nhe1。方法：在HL-1心肌细胞和缺乏功能性Sgk1的基因靶向小鼠（sgk1 -/-）和相应的野生型小鼠（sgk1 + / + ）中进行实验。通过定量RT-PCR确定基因表达，并使用针对P-Ser 703 处的14-3-3结合基序的特异性抗体确定Nhe1磷酸化，该抗体代表Sgk1的假定的磷酸化位点识别基序并参与Nhe1激活。 Na 2活性是利用2'，7'-双-（2-羧乙基）-5-（和-6）-羧基荧光素（BCECF）荧光和Nhe活性确定的胞质pH（pH i ）。铵脉冲后sup> + 依赖的碱化。结果：地塞米松治疗HL-1心肌细胞后，Sgk1 mRNA表达显着增加，同时Na + / H + 交换子活性增加。此外，地塞米松显着增加Nhe1和Spp1 mRNA表达。 HL-1心肌细胞与Sgk1抑制剂EMD638683共同处理会削弱地塞米松的作用。与Nhe1抑制剂cariporide共同治疗可类似地阻止地塞米松刺激的Spp1 mRNA表达。在sgk1 + / + 小鼠中，地塞米松显着增加了心脏Sgk1 mRNA水平。在sgk1 + / + 小鼠中，而不是sgk1 -/-小鼠中，地塞米松显着增加Ser 703 时心脏Nhe1 mRNA表达和Nhe1磷酸化。此外，在地塞米松治疗的sgk1 + / + 小鼠中，心脏Spp1，Ctgf，Nppa和Nppb mRNA水平显着增加，而在sgk1 -//-小鼠中，这种作用明显减弱。结论：Sgk1参与心脏Na + / H + 交换子Nhe1的磷酸化和激活。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号