Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium channels via a nongenomic pathway of sex hormones
Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium channels via a nongenomic pathway of sex hormones
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DOI：
10.1124/mol.106.028134
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发表时间：
2006-12-01
影响因子：
3.6
通讯作者：
Kurokawa, Junko
中科院分区：
文献类型：
--
作者：
Furukawa, Tetsushi;Bai, Chang-Xi;Kurokawa, Junko
人参根是世界上最受欢迎的草药之一，被认为是一种灵丹妙药，可以促进长寿。它已被用作预防心脏缺血的药物，心脏缺血是西方死亡的主要原因。我们以前已经证明，人参的主要植物甾醇，人参皂苷Re，抑制心肌缺血/再灌注过程中线粒体Ca ~（2+）的积累，这归因于一氧化氮（NO）诱导的心肌细胞Ca ~（2+）通道抑制和K ~+通道激活。在这项研究中，我们提供了令人信服的证据表明，RextiRe激活内皮NO合酶（eNOS）释放NO，导致激活的缓慢激活延迟整流K+电流。eNOS激活通过雄激素受体、雌激素受体-α和孕激素受体中的每一种的非基因组途径发生，其中c-Src、磷酸肌醇3-激酶、Akt和eNOS依次被激活。然而，C57 Re不刺激雄激素响应性LNCaP细胞和雌激素响应性MCF-7细胞的增殖，这意味着C57 Re不激活性激素受体的基因组途径。使用探针SCCoR（单细胞辅激活因子募集）进行的荧光共振能量转移实验表明，基因组作用的缺乏归因于辅激活因子募集的失败。因此，EPORe作为性类固醇受体的非基因组途径的特异性激动剂，并且从激活的eNOS释放的NO是心脏K+通道激活和对缺血-再灌注损伤的保护的基础。
Ginseng root is one of the most popular herbs throughout the world and is believed to be a panacea and to promote longevity. It has been used as a medicine to protect against cardiac ischemia, a major cause of death in the West. We have previously demonstrated that ginsenoside Re, a main phytosterol of Panax ginseng, inhibits Ca2+ accumulation in mitochondria during cardiac ischemia/reperfusion, which is attributable to nitric oxide (NO)-induced Ca2+ channel inhibition and K+ channel activation in cardiac myocytes. In this study, we provide compelling evidence that ginsenoside Re activates endothelial NO synthase (eNOS) to release NO, resulting in activation of the slowly activating delayed rectifier K+ current. The eNOS activation occurs via a nongenomic pathway of each of androgen receptor, estrogen receptor-alpha, and progesterone receptor, in which c-Src, phosphoinositide 3-kinase, Akt, and eNOS are sequentially activated. However, ginsenoside Re does not stimulate proliferation of androgen-responsive LNCaP cells and estrogen-responsive MCF-7 cells, implying that ginsenoside Re does not activate a genomic pathway of sex hormone receptors. Fluorescence resonance energy transfer experiments with a probe, SCCoR (single cell coactivator recruitment), indicate that the lack of genomic action is attributable to failure of coactivator recruitment. Thus, ginsenoside Re acts as a specific agonist for the nongenomic pathway of sex steroid receptors, and NO released from activated eNOS underlies cardiac K+ channel activation and protection against ischemia-reperfusion injury.