Pakharukova N A, Pastushkova L Kh, Moshkovskiĭ S A, Larina I M
Biomed Khim. 2012 Sep-Oct;58(5):514-29. doi: 10.18097/pbmc20125805514.
The purpose of this review is to analyze investigations devoted to characteristic of protein variability and diversity of their posttranslational modifications in healthy humans. The numerous researches have demonstrated that proteomic profile has a considerable both intra- and inter-individual variability, and quite often normal variability of some proteins can be comparable to changes observed in pathological processes. Results obtained by our research group have confirmed high intra-individual variability of serum low-molecular subproteome of healthy volunteers, certified by a special medial committee. Proteins characterized by high variability in normal conditions (e.g. haptoglobin--0-40 mg/ml; lysozyme--0,01-0,1 mg/ml; C-reactive protein--0,01-0,3 mg/ml) should be excluded from the list of potential biomarkers. On the contrary, proteins and peptides characterized by insignificant dispersion in healthy population (such as albumin--coefficient of variation (CV) 9%; transferrin--CV14%; C3c complement--CV 17%, alpha-1 acid glycoprotein--CV 21%, alpha2-macroglobulin--CV 20%; transthyretin fragment--CV 28,3% and beta-chain alpha2-HS-glycoprotein--CV 29,7%) can provide us with important information about state of health. Thus investigations of plasticity in proteomic profiles of healthy humans will help to correct reference intervals used in clinical proteomics.
本综述的目的是分析针对健康人体内蛋白质变异性及其翻译后修饰多样性特征的研究。众多研究表明,蛋白质组学图谱在个体内和个体间都具有相当大的变异性,而且某些蛋白质的正常变异性往往可与病理过程中观察到的变化相媲美。我们研究小组获得的结果证实了健康志愿者血清低分子亚蛋白质组具有较高的个体内变异性,这一点得到了一个特别医学委员会的认证。在正常情况下具有高变异性的蛋白质(例如触珠蛋白——0 - 40毫克/毫升;溶菌酶——0.01 - 0.1毫克/毫升;C反应蛋白——0.01 - 0.3毫克/毫升)应从潜在生物标志物列表中排除。相反,在健康人群中离散度较小的蛋白质和肽(如白蛋白——变异系数(CV)9%;转铁蛋白——CV 14%;C3c补体——CV 17%,α1酸性糖蛋白——CV 21%,α2巨球蛋白——CV 20%;转甲状腺素蛋白片段——CV 28.3%以及β链α2 - HS - 糖蛋白——CV 29.7%)能够为我们提供有关健康状况的重要信息。因此,对健康人蛋白质组学图谱可塑性的研究将有助于校正临床蛋白质组学中使用的参考区间。