Fo Shou San, an Ancient Herbal Decoction Prepared from Angelicae Sinensis Radix and Chuanxiong Rhizoma, Induces Erythropoietin Expression: A Signaling Mediated by the Reduced Degradation of Hypoxia-Inducible Factor in Cultured Liver Cells
Fo Shou San, an Ancient Herbal Decoction Prepared from Angelicae Sinensis Radix and Chuanxiong Rhizoma, Induces Erythropoietin Expression: A Signaling Mediated by the Reduced Degradation of Hypoxia-Inducible Factor in Cultured Liver Cells
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DOI：
10.1055/s-0031-1280356
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发表时间：
2012-01-01
期刊：
影响因子：
2.7
通讯作者：
Tsim, Karl W. K.
中科院分区：
文献类型：
--
作者：
Bi, Cathy W. C.;Xu, Li;Tsim, Karl W. K.
火寿散（FSS）是由当归与川芎按3:2的比例配制而成的一种古老的中药汤剂。FSS主要用于血液供应不足的患者，它确实已被证明可以刺激培养细胞中促红细胞生成素（EPO）的产生。为了揭示fss诱导EPO基因表达的机制，我们在培养的肝癌细胞系Hep3B中，通过缺氧诱导的信号传导，揭示了上游调控级联。在培养的肝细胞中，FSS诱导EPO基因表达：(1)EPO mRNA表达增加；（ii）缺氧反应元件（HRE）的激活，这是EPO基因的上游调节因子。fss诱导的EPO基因表达是由缺氧诱导因子-1 α (HIF-1 α)蛋白表达增加触发的；然而，FSS处理未改变HIF-1 α mRNA的表达。增加的HIF-1 α是FSS处理后蛋白质降解减少的结果。因此，目前的结果提供了这种古老的草药汤剂的造血功能的分子机制之一。
Fo Shou San (FSS) is an ancient herbal decoction composed of Angelicae Sinensis Radix (ASR; Danggui) and Chuanxiong Rhizoma (CR; Chuanxiong) in a ratio of 3:2. FSS is mainly prescribed for patients having a deficiency of blood supply, and it indeed has been shown to stimulate the production of erythropoietin (EPO) in cultured cells. In order to reveal the mechanism of this FSS-induced EPO gene expression, the upstream regulatory cascade, via hypoxia-induced signaling, was revealed here in cultured hepatocellular carcinoma cell line Hep3B. The induction of EPO gene expression, triggered by FSS, was revealed in cultured hepatocytes by: (i) the increase of EPO mRNA; and (ii) the activation of the hypoxia response element (HRE), an upstream regulator of the EPO gene. The FSS-induced EPO gene expression was triggered by an increased expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein; however, the mRNA expression of HIF-1 alpha was not altered by the treatment of FSS. The increased HIF-1 alpha was a result of reduced protein degradation after the FSS treatment. The current results therefore provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.