ERYTHROPOIETIN - GENE CLONING, PROTEIN-STRUCTURE, AND BIOLOGICAL PROPERTIES
ERYTHROPOIETIN - GENE CLONING, PROTEIN-STRUCTURE, AND BIOLOGICAL PROPERTIES
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DOI：
10.1101/sqb.1986.051.01.082
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发表时间：
1986-01-01
期刊：
影响因子：
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通讯作者：
STEBBING, N
中科院分区：
文献类型：
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作者：
BROWNE, JK;COHEN, AM;STEBBING, N
人促红细胞生成素（EPO）基因的成功克隆（Jacobs等，1985; Lin等，1985）已经获得了关于这种激素的遗传组织和蛋白质结构的信息，并允许对其生物学特性进行评估。生物学研究已经清楚地表明了这种激素在治疗各种贫血中的临床潜力，并且重组DNA产生的人EPO（r-hEPO）1的初步临床研究现在正在进行中。EPO是一种唾液酸糖蛋白激素，负责调节红细胞形成速率和维持红细胞质量（Krantz and Jacobson 1970; Graber and Krantz 1978; Spivak and Graber 1980）。EPO主要由成人的肾脏和胎儿期的肝脏产生，并分泌到循环中（Jacobsen et al. 1957; Fried 1972; Zanjani et al. 1981）。EPO的循环水平约为20 mU/ml（Koeffler and Goldwasser 1981; Cotes 1982; Garcia et al. 1982）。EPO的血清水平在组织缺氧条件下升高，在高氧条件下降低。肾脏通过增加EPO产生速率对贫血作出反应，导致血清EPO水平增加多达100倍（Adenbach和Adamson 1985）。慢性肾衰竭中发现的肾脏损伤导致贫血，主要是由于EPO产生不足（Brown 1965; Naets 1975; Erslev et al. 1980）。虽然EPO是在世纪之交提出的（Carnat和Defandre 1906），但在1971年首次从贫血绵羊血浆中部分纯化（Goldwasser和Kung 1971）。1977年，人EPO首次从再生障碍性贫血患者的尿液中纯化至均一（Miyake等，1977）。纯化的人尿EPO具有约34，000的表观分子量，并可分离成两种形式，称为α和β，其碳水化合物含量不同（Dordal等，1985）。据报道，纯化的人尿EPO的比活性为70，000 U/mg（Miyake等人，1977）。
The successful cloning of the gene for human erythropoietin (EPO)(Jacobs et al. 1985; Lin et al. 1985) has yielded information on the genetic organization and protein structure of this hormone and has allowed assessment of its biological properties. Biological studies have clearly indicated the clinical potential for this hormone in treatment of various anemias, and initial clinical studies of recombinant-DNA-produced human EPO (r-hEPO) 1 are now under way. EPO, a sialylglycoprotein hormone, is responsible for regulating the rate of red blood cell formation and for maintaining the red blood cell mass (Krantz and Jacobson 1970; Graber and Krantz 1978; Spivak and Graber 1980). EPO is produced primarily by the kidney in adults and by the liver during fetal life and is secreted into the circulation (Jacobsen et al. 1957; Fried 1972; Zanjani et al. 1981). Circulating levels of EPO are approximately 20 mU/ml (Koeffler and Goldwasser 1981; Cotes 1982; Garcia et al. 1982). Serum levels of EPO increase under conditions of tissue hypoxia and decrease under conditions of hyperoxia. The kidney responds to anemia by increasing the rate of EPO production, resulting in an increase of as much as 100-fold in serum EPO levels (Eschbach and Adamson 1985). Damage to the kidney, as found in chronic renal failure, results in anemia primarily due to a deficiency in EPO production (Brown 1965; Naets 1975; Erslev et al. 1980). Although postulated at the turn of the century (Carnat and Defandre 1906), EPO was first partially purified in 1971 from anemic sheep plasma (Goldwasser and Kung 1971). Human EPO was first purified to homogeneity in 1977 from the urine of aplastic anemia patients (Miyake et al. 1977). Purified human urinary EPO has an apparent molecular weight of about 34,000 and can be separated into two forms, termed a and/~, which differ in their carbohydrate content (Dordal et al. 1985). A specific activity of 70,000 U/mg has been reported for purified human urinary EPO (Miyake et al. 1977).