Stimulating Effect of Ethanol on Erythropoietin Production in the Liver Cells
Stimulating Effect of Ethanol on Erythropoietin Production in the Liver Cells
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DOI：
10.4172/2167-0943.1000164
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
K. Nishimura;H. Katuyama;H. Nakagawa;Saburo Matuo
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文献类型：
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作者：
K. Nishimura;H. Katuyama;H. Nakagawa;Saburo Matuo
促红细胞生成素 (EPO) 产量的增加对于红细胞生成和细胞活力非常重要。促进EPO产生的最有效因素是缺氧，它会改变氧化还原状态并在细胞内产生还原环境。在本研究中，我们检查了乙醇对 HepG2 细胞中 EPO 产生的影响，以研究常氧条件下增加细胞质中游离 NADH/NAD+ 比率的效果。乙醇处理以剂量依赖性方式增加了乳酸/丙酮酸比率（细胞质氧化还原状态的指数），在 300 μM 乙醇下观察到最大促进 EPO 产生。这些结果表明，将细胞质 NADH/NAD+ 氧化还原状态改变至与缺氧相同的程度可有效促进 EPO 产生。乙醇 (300 μM) 增加了 Sirtuin1 的 mRNA 表达和蛋白质水平，sirtuin1 是一种转录因子，与缺氧诱导因子和细胞质氧化还原状态相关，而 2000 μM 乙醇则不会产生这些作用。尽管sirtuin1抑制剂EX-527不影响乳酸/丙酮酸比率，但EX-527抑制300 μM乙醇对EPO mRNA表达的诱导。在大鼠原代肝细胞和肾细胞中，300 μM 乙醇增加了 Sirtuin1 和 EPO mRNA 表达，以及培养基中 EPO 浓度。总之，我们发现低浓度乙醇通过增加 HepG2 细胞以及原代肝细胞和肾细胞中的 Sirtuin1 来促进 EPO 产生。使用乙醇代表了一种不依赖缺氧的促进 EPO 产生的方法。
Increased erythropoietin (EPO) production is important for erythropoiesis as well as cell viability. The most effective factor for promoting EPO production is hypoxia, which alters the redox state and produces a reducing environment in the cell. In this study, we examined the influence of ethanol on EPO production in HepG2 cells to investigate the effect of increasing the free NADH/NAD+ ratio in the cytosol during normoxia. Ethanol treatment increased the lactate/pyruvate ratio, an index of the cytosolic redox state, in a dose-dependent manner, with maximal promotion of EPO production observed at 300 μM ethanol. These results suggest that altering the cytosolic NADH/NAD+ redox state to the same degree as hypoxia is effective in promoting EPO production. Ethanol (300 μM) increased mRNA expression and protein levels of sirtuin1, which is a transcription factor, related to both hypoxia inducible factor and cytosolic redox state, whereas 2000 μM ethanol did not produce these effects. Although the sirtuin1 inhibitorEX-527 did not affect the lactate/pyruvate ratio, EX-527 inhibited the induction of EPO mRNA expression by 300 μM ethanol. In rat primary hepatocytes and kidney cells, 300 μM ethanol increased sirtuin1 and EPO mRNA expression, as well as EPO concentrations in media. In conclusion, we showed low concentrations of ethanol promote EPO production by increasing sirtuin1 in HepG2 cells, as well as primary liver and kidney cells. The use of ethanol represents a hypoxia-independent method to promote EPO production.