Fisher J W
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Proc Soc Exp Biol Med. 1997 Dec;216(3):358-69. doi: 10.3181/00379727-216-44183.
The purpose of this review is to give an update of the recent progress in research on erythropoietin (Epo), the hormone that regulates red blood cell production. Epo is a glycoprotein with a molecular mass of approx 30 kDa, which circulates in plasma of the human with 165 amino acids with three N-linked and one O-linked acidic oligosaccharide side chains in the molecule. Both the alpha (39% CHO) and beta (24% CHO) forms are available for clinical use, and there does not appear to be any difference in the pharmacokinetics of these two forms of Epo. Radioimmunoassays and enzyme-linked immunoabsorbant (ELISA) assays are available in a kit form. Serum levels of Epo in normal human subjects range between 1 and 27 mmu/ml or approx 5 pmol/l. It seems clear that the cells in the adult mammalian kidney which produce Epo are the interstitial cells in the peritubular capillary bed and the perivenous hepatocytes in the liver. Expression of the human Epo gene sequences that direct expression in the kidney are located 6-14 kilobases 5' to the gene; whereas the sequences that control hepatocyte-specific expression are located within 0.7 KS to the 3'-flanking region and 0.5 KS to the 5'-flanking region. The signal transduction pathways postulated to be involved in the expression of Epo are: kinases A, G and C; both a constitutive factor and a second hypoxia-inducible factor-1 (HIF-1) located in the 5' end of an hypoxia inducible enhancer region of the Epo gene; and reactive oxygen species. The primary target cell in the bone marrow acted on by Epo is the colony-forming unit erythroid (CFU-E) which has the highest number of Epo receptors. It has been postulated that Epo decreases the rate which Epo-dependent progenitor cells undergo programed cell death (apoptosis). There are two major signal transduction pathways activated by the Epo receptor: the JAK2-STAT5 pathway and the ras pathway. Both pathways involve tyrosine phosphorylation. The approved clinical uses of Epo are the anemias associated with end-stage renal disease, cancer chemotherapeutic agents, and patients with HIV infection receiving AZT. Other anemias reported to respond to Epo therapy are anemia of prematurity, rheumatoid arthritis, and myelodysplasia. Other uses of Epo under investigation are in perioperative surgery and preoperative autologous blood donation.
本综述的目的是介绍促红细胞生成素（Epo）研究的最新进展，Epo是一种调节红细胞生成的激素。Epo是一种糖蛋白，分子量约为30 kDa，在人体血浆中循环，分子中有165个氨基酸以及三条N-连接和一条O-连接的酸性寡糖侧链。α（39% 碳水化合物）和β（24% 碳水化合物）两种形式均可用于临床，这两种形式的Epo在药代动力学上似乎没有差异。放射免疫测定法和酶联免疫吸附测定法（ELISA）都有试剂盒形式。正常人类受试者的血清Epo水平在1至27 mU/ml之间，即约5 pmol/l。很明显，成年哺乳动物肾脏中产生Epo的细胞是肾小管周围毛细血管床的间质细胞和肝脏中的肝静脉周围肝细胞。指导在肾脏中表达的人类Epo基因序列位于该基因5'端6 - 14千碱基处；而控制肝细胞特异性表达的序列位于3'侧翼区域0.
