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Impaired Biological Activity of Erythropoietin by Cyanate Carbamylation

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Author(s)
Kyo-Cheol MunThomas A. Golper
Keimyung Author(s)
Mun, Kyo Cheol
Department
Dept. of Biochemistry (생화학)
Journal Title
Blood Purification
Issued Date
2000
Volume
18
Issue
1
Abstract
AIMS: During advanced renal failure, particularly in patients with end-stage renal disease (ESRD), proteins are carbamylated as a result of a reaction with cyanate. Some or all of the cyanate is derived from urea. If the carbamylation of proteins adversely alters their biologic activities, then urea must be viewed as an uremic toxin, rather than a surrogate. Therefore, we studied the effect of cyanate carbamylation on the erythropoietic activity of erythropoietin (EPO) in a rodent model.

METHODS: EPO was carbamylated by incubation with cyanate at 37 degrees C. The extent of carbamylation was monitored using trinitrobenzenesulfonic acid. In Sprague-Dawley rats the erythrocyte count, hemoglobin concentration, and hematocrit were measured after the twice-weekly subcutaneous injection of either EPO or carbamylated EPO for 3 weeks. Two additional control groups received physiologic saline or 0.2 ml of 1 M cyanate.

RESULTS: The level of carbamylated EPO was increased as the time of exposure to cyanate increased from 1 to 6 h, and as the cyanate concentration increased from 8 to 2,000 mM. EPO injections caused significantly large increases in all erythropoietic measures. Physiologic saline or 1 M cyanate-injected controls and the carbamylated EPO-injected animals demonstrated no change from baseline in erythropoietic parameters.

CONCLUSION:

These results support that EPO exposed to high levels of cyanate in vitro demonstrates diminished biologic activity in healthy Sprague-Dawley rats. This effect may be manifested by the carbamylation of EPO by the cyanate. Should this occur in ESRD patients, it may contribute to the suboptimal erythropoietic response to EPO therapy associated with high urea levels, especially related to inadequate dialysis. Targeting dialysis doses specifically to urea concentrations may be more important than previously considered.
Key Words
Urea W Carbamylation W Cyanate W Erythropoietin W
Dialysis
Keimyung Author(s)(Kor)
문교철
Publisher
School of Medicine
Citation
Kyo-Cheol Mun and Thomas A. Golper. (2000). Impaired Biological Activity of Erythropoietin by Cyanate Carbamylation. Blood Purification, 18(1), 13–17. doi: 10.1159/000014403
Type
Article
ISSN
0253-5068
Source
http://lps3.www.karger.com.proxy.dsmc.or.kr/Article/Abstract/14403
DOI
10.1159/000014403
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35230
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
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