Inoue N, Takeuchi M, Ohashi H, Suzuki T
Central Laboratories for Key Technology, Kirin Brewery Co. Ltd., Kanagawa, Japan.
Biotechnol Annu Rev. 1995;1:297-313. doi: 10.1016/s1387-2656(08)70055-3.
Erythropoietin (EPO) is the glycoprotein hormone that promotes differentiation of erythroid progenitor cells in bone marrow. The normal kidney produces EPO to maintain erythrocyte for oxygen supply. This hormone activity was found in the serum of anemic animals in the 1890s. Renal failure results in severe anemia because of reduced EPO production, therefore anemia patients expected EPO treatment for long time. However, this was difficult due to the limited amount of EPO. Many researchers have tried to isolate EPO since the 1950s. Finally Miyake and Goldwasser purified highly active EPO from the urine of aplastic anemia patients. Since then, the characteristics and structural information from the purified material accelerated the cloning of the EPO gene. Mammalian cells were essential to produce EPO, because EPO contains 40% carbohydrate that plays some important roles in its activity, stability and biosynthesis. In 1984, two groups succeeded in cloning the EPO gene and expressing this gene in mammalian cells. Recombinant human EPO is currently available for anemia treatment. In this paper, we review production in mammalian cells, molecular characterization, especially carbohydrate moieties, and clinical applications of recombinant EPO.
促红细胞生成素（EPO）是一种糖蛋白激素，可促进骨髓中红系祖细胞的分化。正常肾脏产生EPO以维持红细胞数量，从而保证氧气供应。19世纪90年代，人们在贫血动物的血清中发现了这种激素的活性。肾衰竭会因EPO生成减少而导致严重贫血，因此贫血患者长期以来都期望能接受EPO治疗。然而，由于EPO的量有限，这一期望难以实现。自20世纪50年代以来，许多研究人员都试图分离EPO。最终，三宅和戈德瓦塞尔从再生障碍性贫血患者的尿液中纯化出了高活性的EPO。从那时起，纯化物质的特性和结构信息加速了EPO基因的克隆。由于EPO含有40%的碳水化合物，这些碳水化合物在其活性、稳定性和生物合成中发挥着重要作用，因此哺乳动物细胞对于生产EPO至关重要。1984年，两个研究小组成功克隆了EPO基因，并在哺乳动物细胞中表达了该基因。重组人促红细胞生成素目前可用于治疗贫血。在本文中，我们综述了重组促红细胞生成素在哺乳动物细胞中的生产、分子特征，尤其是碳水化合物部分，以及其临床应用。
