Rhodiola crenulata and Its Bioactive Components, Salidroside and Tyrosol, Reverse the Hypoxia-Induced Reduction of Plasma-Membrane-Associated Na,K-ATPase Expression via Inhibition of ROS-AMPK-PKC ξ Pathway.

Rhodiola crenulata and Its Bioactive Components, Salidroside and Tyrosol, Reverse the Hypoxia-Induced Reduction of Plasma-Membrane-Associated Na,K-ATPase Expression via Inhibition of ROS-AMPK-PKC ξ Pathway.
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Rhodiola crenulata及其生物活性成分,盐酸和酪醇,通过抑制ROS-AMPK-PKC途径抑制缺氧引起的血浆膜相关Na,K-ATPase表达的减少。

DOI:
10.1155/2013/284150
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发表时间:
2013
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Chang TC
Chang TC
中科院分区:
其他
文献类型:
--
作者:
Lee SY;Shi LS;Chu H;Li MH;Ho CW;Lai FY;Huang CY;Chang TC

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暴露于缺氧导致肺钠转运受损,这与肺泡上皮Na, k - atp酶功能障碍有关。本研究旨在探讨红景天提取物(RCE)及其活性成分对缺氧介导的Na, k - atp酶内吞作用的影响及其机制。A549细胞在RCE、红景天苷或酪醇存在或不存在的情况下暴露于缺氧。采用荧光探针DCFH-DA检测细胞内ROS的生成,通过测定PM组分中Na, k - atp酶的表达水平来检测细胞内吞作用。采用低气压缺氧舱大鼠,研究RCE在体内的作用及其机制。我们的研究结果表明,RCE及其生物活性化合物通过抑制ROS-AMPK-PKCζ通路在A549细胞中显著阻止缺氧介导的Na, k - atp酶内吞。此外,RCE在啮齿动物模型中对Na、k - atp酶内吞和AMPK-PKCξ通路的抑制也有相当的预防作用。我们的研究首次提供了大量证据来支持红景天产品对低氧相关Na, k - atp酶内吞作用的有效性,并阐明了红景天作为一种流行的高原疾病民间药物的民族药理学相关性。
Exposure to hypoxia leads to impaired pulmonary sodium transport, which is associated with Na,K-ATPase dysfunction in the alveolar epithelium. The present study is designed to examine the effect and mechanism of Rhodiola crenulata extract (RCE) and its bioactive components on hypoxia-mediated Na,K-ATPase endocytosis. A549 cells were exposed to hypoxia in the presence or absence of RCE, salidroside, or tyrosol. The generation of intracellular ROS was measured by using the fluorescent probe DCFH-DA, and the endocytosis was determined by measuring the expression level of Na,K-ATPase in the PM fraction. Rats exposed to a hypobaric hypoxia chamber were used to investigate the efficacy and underlying mechanism of RCE in vivo. Our results showed that RCE and its bioactive compounds significantly prevented the hypoxia-mediated endocytosis of Na,K-ATPase via the inhibition of the ROS-AMPK-PKCζ pathway in A549 cells. Furthermore, RCE also showed a comparable preventive effect on the reduction of Na,K-ATPase endocytosis and inhibition of AMPK-PKCξ pathway in the rodent model. Our study is the first to offer substantial evidence to support the efficacy of Rhodiola products against hypoxia-associated Na,K-ATPase endocytosis and clarify the ethnopharmacological relevance of Rhodiola crenulata as a popular folk medicine for high-altitude illness.
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