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Novel serum biomarkers for erythropoietin use in humans: a proteomic approach


Christensen, Britt; Sackmann-Sala, L; Cruz-Topete, D; Jørgensen, J O L; Jessen, N; Lundby, C; Kopchick, J J (2011). Novel serum biomarkers for erythropoietin use in humans: a proteomic approach. Journal of Applied Physiology, 110(1):149-156.

Abstract

Erythropoietin (Epo) is produced primarily in the kidneys upon low blood oxygen availability and stimulates erythropoiesis in the bone marrow. Recombinant human Epo (rHuEpo), a drug developed to increase arterial oxygen content in patients, is also illicitly used by athletes to improve their endurance performance. Therefore, a robust and sensitive test to detect its abuse is needed. The aim of the present study was to investigate potential human serum biomarkers of Epo abuse employing a proteomic approach. Eight healthy male subjects were injected subcutaneously with rHuEpo (5,000 IU) every second day for a 16-day period. Serum was collected before starting the treatment regime and again at days 8 and 16 during the treatment period. Samples were homogenized and proteins separated by two-dimensional gel electrophoresis (2DE). Spots that changed significantly in response to rHuEpo treatment were identified by mass spectrometry. Both the number of reticulocytes and erythrocytes increased throughout the study, leading to a significant increase in hematocrit and hemoglobin content. In addition, transferrin levels increased but the percentage of iron bound to transferrin and ferritin levels decreased. Out of 97 serum proteins, seven were found to decrease significantly at day 16 compared with pre-Epo administration, and were identified as four isoforms of haptoglobin, two isoforms of transferrin, and a mixture of hemopexin and albumin. In support, total serum haptoglobin levels were found to be significantly decreased at both days 8 and 16. Thus a 2DE proteomic approach for discovery of novel markers of Epo action appears feasible.

Erythropoietin (Epo) is produced primarily in the kidneys upon low blood oxygen availability and stimulates erythropoiesis in the bone marrow. Recombinant human Epo (rHuEpo), a drug developed to increase arterial oxygen content in patients, is also illicitly used by athletes to improve their endurance performance. Therefore, a robust and sensitive test to detect its abuse is needed. The aim of the present study was to investigate potential human serum biomarkers of Epo abuse employing a proteomic approach. Eight healthy male subjects were injected subcutaneously with rHuEpo (5,000 IU) every second day for a 16-day period. Serum was collected before starting the treatment regime and again at days 8 and 16 during the treatment period. Samples were homogenized and proteins separated by two-dimensional gel electrophoresis (2DE). Spots that changed significantly in response to rHuEpo treatment were identified by mass spectrometry. Both the number of reticulocytes and erythrocytes increased throughout the study, leading to a significant increase in hematocrit and hemoglobin content. In addition, transferrin levels increased but the percentage of iron bound to transferrin and ferritin levels decreased. Out of 97 serum proteins, seven were found to decrease significantly at day 16 compared with pre-Epo administration, and were identified as four isoforms of haptoglobin, two isoforms of transferrin, and a mixture of hemopexin and albumin. In support, total serum haptoglobin levels were found to be significantly decreased at both days 8 and 16. Thus a 2DE proteomic approach for discovery of novel markers of Epo action appears feasible.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:January 2011
Deposited On:04 Feb 2011 14:21
Last Modified:05 Apr 2016 14:43
Publisher:American Physiological Society
ISSN:0161-7567
Publisher DOI:10.1152/japplphysiol.00665.2010
PubMed ID:20966191
Permanent URL: http://doi.org/10.5167/uzh-44589

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