PMID- 9402140
OWN - NLM
STAT- MEDLINE
DCOM- 19971223
LR  - 20200930
IS  - 0037-9727 (Print)
IS  - 0037-9727 (Linking)
VI  - 216
IP  - 3
DP  - 1997 Dec
TI  - Erythropoietin: physiologic and pharmacologic aspects.
PG  - 358-69
AB  - 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.
FAU - Fisher, J W
AU  - Fisher JW
AD  - Department of Pharmacology, Tulane University School of Medicine, New Orleans, 
      Louisiana 70112, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Proc Soc Exp Biol Med
JT  - Proceedings of the Society for Experimental Biology and Medicine. Society for 
      Experimental Biology and Medicine (New York, N.Y.)
JID - 7505892
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Erythropoietin/biosynthesis/chemistry/*pharmacology/*physiology/standards/therapeutic 
      use
MH  - Humans
MH  - Molecular Sequence Data
MH  - Recombinant Proteins
MH  - Signal Transduction
MH  - Structure-Activity Relationship
RF  - 154
EDAT- 1997/12/24 00:00
MHDA- 1997/12/24 00:01
CRDT- 1997/12/24 00:00
PHST- 1997/12/24 00:00 [pubmed]
PHST- 1997/12/24 00:01 [medline]
PHST- 1997/12/24 00:00 [entrez]
AID - 10.3181/00379727-216-44183 [doi]
PST - ppublish
SO  - Proc Soc Exp Biol Med. 1997 Dec;216(3):358-69. doi: 10.3181/00379727-216-44183.