Zhao Mindi, Wu Jianqiang, Gao Youhe
Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Department of Biochemistry and Molecular Biology, Beijing Normal University, Gene Engineering and Biotechnology Beijing Key Laboratory, Beijing, China.
PLoS One. 2016 Oct 25;11(10):e0164796. doi: 10.1371/journal.pone.0164796. eCollection 2016.
Urine, reflecting many changes in the body, is a better source than blood for biomarker discovery. However, even under physiological conditions, the urine proteome often varies. Understanding how various regulating factors affect urine proteome helps link changes to urine proteome with urinary biomarkers of physiological conditions as well as corresponding diseases. To evaluate the possible impact of α1-adrenergic receptor on urine proteome, this study investigated effects of the specific inhibitor prazosin on the urine proteome in a rat model by using tandem mass tagging and two-dimensional liquid chromatography-tandem mass spectrometry. A total of 775 proteins were identified, approximately half of which were influenced by prazosin treatment, indicating that the sympathetic nervous system exerts a significant impact on urine proteome. Eight significantly changed proteins were previously annotated as urinary candidate biomarkers. Angiotensinogen, haptoglobin, and beta-2 microglobulin, which were reported to be associated with blood pressure, were validated via Western blot. Prazosin is widely used in clinical practice; thus, these protein changes should be considered when studying corresponding diseases such as hypertension, post-traumatic stress disorder and benign prostatic hyperplasia. The related physiological activities of α1-receptors, controlling blood pressure and fear response might significantly affect the urine proteome and warrant further biomarker studies.
尿液反映了身体的许多变化，是比血液更好的生物标志物发现来源。然而，即使在生理条件下，尿液蛋白质组也常常变化。了解各种调节因素如何影响尿液蛋白质组，有助于将尿液蛋白质组的变化与生理状况以及相应疾病的尿液生物标志物联系起来。为了评估α1 - 肾上腺素能受体对尿液蛋白质组的可能影响，本研究通过串联质量标签和二维液相色谱 - 串联质谱法，在大鼠模型中研究了特异性抑制剂哌唑嗪对尿液蛋白质组的影响。共鉴定出775种蛋白质，其中约一半受哌唑嗪处理的影响，这表明交感神经系统对尿液蛋白质组有显著影响。八种显著变化的蛋白质先前被注释为尿液候选生物标志物。通过蛋白质印迹法验证了据报道与血压相关的血管紧张素原、触珠蛋白和β2微球蛋白。哌唑嗪在临床实践中广泛使用；因此，在研究诸如高血压、创伤后应激障碍和良性前列腺增生等相应疾病时，应考虑这些蛋白质变化。α1受体控制血压和恐惧反应的相关生理活动可能会显著影响尿液蛋白质组，值得进一步进行生物标志物研究。
