New Transcriptomic Biomarkers for Detection of the Recombinant Human Erythropoietin (rHuEPO) MirCERA in Horses.

IF 2.6 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Drug Testing and Analysis Pub Date : 2024-09-25 DOI:10.1002/dta.3812
Benoit Loup, François André, Nicolas Leuenberger, Alexandre Marchand, Agnès Barnabé, Vivian Delcourt, Patrice Garcia, Marie-Agnès Popot, Ludovic Bailly-Chouriberry
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Abstract

Detection and monitoring of biomarkers related to doping is particularly suitable for the development of analytical strategies dedicated to indirect detection of banned substances. Previous studies in horses have already allowed the investigation of transcriptomic biomarkers in equine blood associated with reGH and rHuEPO administrations. Our most recent developments continue to focus on the discovery and monitoring of transcriptomic biomarkers for the control of ESAs, and a collaborative study with WADA-accredited doping control laboratories has recently been initiated to conduct a pilot study. In humans, three mRNAs (ALAS2, CA1, and SLC4A1) were previously observed to be differentially expressed after blood doping and were associated with immature red blood cells, the so-called circulating reticulocytes. In horses, circulating reticulocytes are rarely observed even after rHuEPO administration. With the improved primers that detect the equine orthologues of the human mRNAs from the ALAS2, CA1, and SLC4A1 genes, we can now report the first evidence of the detection of the three biomarkers in equine blood. In addition, an upregulation of the mRNA levels of the three genes was observed after analysis of blood samples collected from MirCERA-treated animals, with kinetics similar to those previously documented in humans. Our data suggest that ALAS2 and CA1 are promising indirect biomarkers for the detection of recombinant EPO abuse in horses, as observed in humans.

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用于检测马体内重组人促红细胞生成素 (rHuEPO) MirCERA 的新转录组生物标记物。
检测和监测与使用兴奋剂有关的生物标志物尤其适用于开发用于间接检测禁用物质的分析策略。之前在马匹身上进行的研究已经能够调查马匹血液中与服用再生长激素和 rHuEPO 相关的转录组生物标志物。我们的最新进展仍然集中在发现和监测转录组生物标志物以控制 ESAs,并且最近启动了一项与世界反兴奋剂机构认证的兴奋剂控制实验室的合作研究,以开展试点研究。在人类中,以前曾观察到三种 mRNA(ALAS2、CA1 和 SLC4A1)在使用血液兴奋剂后有不同程度的表达,并与未成熟红细胞(即所谓的循环网织红细胞)有关。在马匹中,即使服用 rHuEPO 后也很少观察到循环网织红细胞。通过改良引物检测人类 ALAS2、CA1 和 SLC4A1 基因 mRNA 的马同源物,我们现在可以首次报告在马血液中检测到这三种生物标志物的证据。此外,在分析从 MirCERA 处理过的动物身上采集的血液样本后,我们还观察到了这三个基因 mRNA 水平的上调,其动力学与之前在人类身上记录的动力学相似。我们的数据表明,ALAS2 和 CA1 是很有前途的间接生物标记物,可用于检测马匹体内重组 EPO 的滥用情况,就像在人类身上观察到的一样。
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来源期刊
Drug Testing and Analysis
Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
5.90
自引率
24.10%
发文量
191
审稿时长
2.3 months
期刊介绍: As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.
期刊最新文献
The 42nd Manfred Donike Workshop on Doping Analysis. Long-Term Excretion of Roxadustat in Urine. New Transcriptomic Biomarkers for Detection of the Recombinant Human Erythropoietin (rHuEPO) MirCERA in Horses. Equine Doping Controls of Thymosin β $$ \beta $$ 4: A Population Study and Strategy for Misuse Detection. Skeletal Muscle Memory: An Update From the Antidoping Perspective.
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