Takeuchi M, Kobata A
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Glycobiology. 1991 Sep;1(4):337-46. doi: 10.1093/glycob/1.4.337.
Erythropoietin (EPO) is a haemopoietic hormone specific to cells of erythroid lineage. EPO has recently become available for the treatment of anaemia as the first human recombinant biomedicine produced in heterologous mammalian cells. Human EPO is characterized by its large carbohydrate chains, which occupy close to 40% of its total mass. These sugar moieties were thought to be important for the biological activity of EPO, but detailed studies were not performed until the structures were elucidated. The variety of roles for the sugar chains were then immediately found once the structures were known. EPO is an excellent model for investigating the roles of sugar chains on glycoproteins, since its gene and its multiple glycoforms are available, as well as sensitive bioassays for testing. In this review, we will first summarize the known sugar chain structures of EPO from different host cells, and then discuss the host-cell dependent and peptide structure-dependent glycosylation of glycoproteins. We will then address how one investigates the roles of sugar chains of glycoproteins, show several examples of such investigations, and discuss the functional roles of HuEPO's sugar chains in its biosynthesis and secretion, its in vitro and in vivo biological activities, and its half-life in blood circulation.
促红细胞生成素（EPO）是一种对红系谱系细胞具有特异性的造血激素。EPO作为第一种在异源哺乳动物细胞中生产的人类重组生物药物，最近已可用于治疗贫血。人EPO的特征在于其庞大的碳水化合物链，这些链占据其总质量的近40%。这些糖部分被认为对EPO的生物活性很重要，但直到其结构被阐明才进行详细研究。一旦结构明确，糖链的多种作用随即被发现。EPO是研究糖链在糖蛋白上作用的一个极佳模型，因为其基因、多种糖型以及用于测试的灵敏生物测定法均可得。在本综述中，我们将首先总结来自不同宿主细胞的EPO的已知糖链结构，然后讨论糖蛋白的宿主细胞依赖性和肽结构依赖性糖基化。接着，我们将阐述如何研究糖蛋白糖链的作用，展示此类研究的几个例子，并讨论人促红细胞生成素糖链在其生物合成和分泌、体外和体内生物活性以及血液循环半衰期方面的功能作用。
