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通过针对硒蛋白P的校准酶联免疫吸附测定法鉴定的硒状态生物标志物中的性别特异性和个体间差异。

Sex-specific and inter-individual differences in biomarkers of selenium status identified by a calibrated ELISA for selenoprotein P.

作者信息

Hybsier Sandra, Schulz Torsten, Wu Zida, Demuth Ilja, Minich Waldemar B, Renko Kostja, Rijntjes Eddy, Köhrle Josef, Strasburger Christian J, Steinhagen-Thiessen Elisabeth, Schomburg Lutz

机构信息

Institute for Experimental Endocrinology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.

ICI-immunochemical intelligence GmbH, Berlin, Germany.

出版信息

Redox Biol. 2017 Apr;11:403-414. doi: 10.1016/j.redox.2016.12.025. Epub 2016 Dec 29.

Abstract

Selenoprotein P (SELENOP) is a liver-derived transporter of selenium (Se) in blood, and a meaningful biomarker of Se status. Se is an essential trace element for the biosynthesis of enzymatically-active selenoproteins, protecting the organism from oxidative damage. The usage of uncalibrated assays hinders the comparability of SELENOP concentrations and their pathophysiological interpretation across different clinical studies. On this account, we established a new sandwich SELENOP-ELISA and calibrated against a standard reference material (SRM1950). The ELISA displays a wide working range (11.6-538.4µg/L), high accuracy (2.9%) and good precision (9.3%). To verify whether SELENOP correlates to total Se and to SELENOP-bound Se, serum samples from healthy subjects and age-selected participants from the Berlin Aging Study II were analyzed by SELENOP-ELISA and Se quantification. SELENOP was affinity-purified and its Se content was determined from a subset of samples. There was a high correlation of total Se and SELENOP concentrations in young and elderly men, and in elderly women, but not in young women, indicating a specific sexual dimorphism in these biomarkers of Se status in young subjects. The Se content of isolated SELENOP was independent of sex and age (mean±SD: 5.4±0.5). By using this calibrated SELENOP-ELISA, prior reports on pathological SELENOP concentrations in diabetes and obesity are challenged as the reported values are outside reasonable limits. Biomarkers of Se status in clinical research need to be measured by validated assays in order to avoid erroneous data and incorrect interpretations, especially when analyzing young women. The Se content of circulating SELENOP differs between individuals and may provide some important diagnostic information on Se metabolism and status.

摘要

硒蛋白P(SELENOP)是血液中一种源自肝脏的硒(Se)转运蛋白,也是硒状态的一个重要生物标志物。硒是酶活性硒蛋白生物合成所必需的微量元素,可保护机体免受氧化损伤。未校准检测方法的使用阻碍了不同临床研究中SELENOP浓度及其病理生理学解释的可比性。基于此,我们建立了一种新的夹心SELENOP-ELISA,并以标准参考物质(SRM1950)进行校准。该ELISA具有较宽的工作范围(11.6 - 538.4μg/L)、高准确度(2.9%)和良好的精密度(9.3%)。为了验证SELENOP是否与总硒以及与SELENOP结合的硒相关,我们通过SELENOP-ELISA和硒定量分析了健康受试者以及柏林衰老研究II中按年龄选择的参与者的血清样本。对SELENOP进行了亲和纯化,并从一部分样本中测定了其硒含量。年轻男性和老年男性以及老年女性中总硒和SELENOP浓度高度相关,但年轻女性中并非如此,这表明在年轻受试者中这些硒状态生物标志物存在特定的性别差异。分离出的SELENOP的硒含量与性别和年龄无关(平均值±标准差:5.4±0.5)。通过使用这种校准后的SELENOP-ELISA,先前关于糖尿病和肥胖症中SELENOP病理浓度的报道受到质疑,因为所报道的值超出了合理范围。临床研究中硒状态的生物标志物需要通过经过验证的检测方法来测量,以避免错误数据和错误解释,尤其是在分析年轻女性时。循环SELENOP的硒含量因人而异,可能会提供一些关于硒代谢和状态的重要诊断信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/436a/5220167/8129cb75a3cd/gr1.jpg

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