• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >PP2B-dependent NO production in the medullary thick ascending limb during diabetes.
【24h】

PP2B-dependent NO production in the medullary thick ascending limb during diabetes.

机译：在糖尿病期间，髓质厚上升肢中PP2B依赖的NO产生。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Calcineurin (PP2B) has recently been shown to be upregulated in the medullary thick ascending limb (mTAL) during diabetes. The mTAL expresses all three isoforms of nitric oxide synthase (NOS), which are subject to phosphoregulation and represent substrates for PP2B. Therefore, we hypothesized that diabetes induces PP2B-dependent upregulation of NOS activity and NO production in the mTAL. Three weeks after injection of streptozotocin (STZ rats) or vehicle (sham rats), mTAL suspensions were prepared for use in functional and biochemical assays. PP2B activity and expression were increased in mTALs from STZ rats compared with sham. Nitrite production was significantly reduced in mTALs from STZ rats compared with sham. However, incubation with the free radical scavenger, tempol, unmasked a significant increase in nitrite production by mTALs from STZ rats. Inhibition of PP2B attenuated the increase in nitrite production and NOS activity evident in mTALs from STZ rats. Analysis of specific NOS isoform activity revealed increased NOS1 and NOS2 activities in mTALs from STZ rats. All three NOS isoform activities were regulated in a PP2B-dependent manner. Western blot analysis detected no differences in NOS isoform expression, although phosphorylation of pThr(495)-NOS3 was significantly reduced in mTALs from STZ rats. Phosphorylation of pSer(852)-NOS1, pSer(633)-NOS3, and pSer(1177)-NOS3 was similar in mTALs from STZ and sham rats. Inhibition of PP2B did not alter the phosphorylation of NOS1 or NOS3 at known sites. In conclusion, while NO bioavailability in mTALs is reduced during diabetes, free radical scavenging with tempol unmasks increased NO production that involves PP2B-dependent activation of NOS1 and NOS2.
机译：最近已证明，钙调神经磷酸酶（PP2B）在糖尿病期间在髓质粗大上升肢体（mTAL）中上调。 mTAL表达一氧化氮合酶（NOS）的所有三种同工型，它们受磷酸化作用并代表PP2B的底物。因此，我们假设糖尿病会诱导mTAL中PP2B依赖性NOS活性和NO产生的上调。注射链脲佐菌素（STZ大鼠）或溶媒（假大鼠）三周后，准备了mTAL悬浮液用于功能和生化分析。与假手术相比，STZ大鼠mTALs的PP2B活性和表达增加。与假手术相比，来自STZ大鼠的mTALs中亚硝酸盐的产生显着减少。然而，与自由基清除剂tempol的孵育揭示了来自STZ大鼠的mTALs亚硝酸盐产量的显着增加。对PP2B的抑制作用减弱了STZ大鼠mTALs中亚硝酸盐产量和NOS活性的增加。对特定NOS同工型活性的分析表明，来自STZ大鼠的mTALs中NOS1和NOS2活性增加。所有这三种NOS亚型活性均以PP2B依赖性方式进行调节。蛋白质印迹分析未检测到NOS亚型表达的差异，尽管来自STZ大鼠的mTALs中pThr（495）-NOS3的磷酸化明显降低。在来自STZ和假大鼠的mTAL中，pSer（852）-NOS1，pSer（633）-NOS3和pSer（1177）-NOS3的磷酸化作用相似。抑制PP2B不会改变已知位点上NOS1或NOS3的磷酸化。总之，尽管糖尿病期间mTALs的NO生物利用度降低，但用tempol清除自由基掩盖了NO产生的增加，这涉及PP2B依赖的NOS1和NOS2活化。

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