Sunde Roger A, Thompson Kevin M, Evenson Jacqueline K, Thompson Britta M
Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, WI 53706, USA.
Exp Biol Med (Maywood). 2009 Nov;234(11):1271-9. doi: 10.3181/0906-RM-182.
Transcript (mRNA) levels are increasingly being used in medicine as molecular biomarkers for disease and disease risk, including use of whole blood as a target tissue for analysis. Development of blood molecular biomarkers for nutritional status, too, has potential application that parallels opportunities in medicine, including providing solid data for individualized nutrition. We previously reported that blood glutathione peroxidase-1 (Gpx1) mRNA was expressed at levels comparable to major tissues in rats and humans. To determine the efficacy of using blood Gpx1 mRNA to assess selenium (Se) status and requirements, we fed graded levels of Se (0-0.3 microg Se/g as selenite) to weanling male rats. Se status was determined by liver Se concentration and selenoenzyme activity, and selenoprotein mRNA abundance in liver and blood was determined by ribonuclease protection analysis. Liver Se and plasma glutathione peroxidase-3 and liver Gpx1 activities indicated that minimal Se requirements were at 0.08 microg Se/g diet. When total RNA was isolated from whole blood, Gpx1 mRNA in Se-deficient rats decreased to 10% of levels in Se-adequate (0.2 microg Se/g diet) rats. With Se supplementation, blood Gpx1 mRNA levels increased sigmoidally to a plateau with a minimum Se requirement of 0.08 microg Se/g diet, whereas glutathione peroxidase-4 mRNA levels were unaffected. Similarly, Gpx1 mRNA in RNA isolated from fractionated red blood cells decreased in Se-deficient rats to 23% of Se-adequate levels, with a minimum Se requirement of 0.09 microg Se/g diet. Additional studies showed that the preponderance of whole blood Gpx1 mRNA arises from erythroid cells, most likely reticulocytes and young erythrocytes. In summary, whole blood selenoprotein mRNA levels can be used as molecular biomarkers for assessing Se requirements, illustrating that whole blood has potential as a target tissue in development of molecular biomarkers for use in nutrition as well as in medicine.
转录本（mRNA）水平在医学上越来越多地被用作疾病和疾病风险的分子生物标志物，包括将全血作为分析的靶组织。用于营养状况的血液分子生物标志物的开发也具有与医学领域类似的潜在应用，包括为个性化营养提供可靠数据。我们之前报道过，大鼠和人类血液中的谷胱甘肽过氧化物酶-1（Gpx1）mRNA表达水平与主要组织相当。为了确定使用血液Gpx1 mRNA评估硒（Se）状态和需求量的有效性，我们给断奶雄性大鼠喂食不同水平的硒（以亚硒酸盐形式，0 - 0.3微克硒/克）。通过肝脏硒浓度和硒酶活性来确定硒状态，通过核糖核酸酶保护分析来测定肝脏和血液中硒蛋白mRNA的丰度。肝脏硒、血浆谷胱甘肽过氧化物酶-3以及肝脏Gpx1活性表明，最低硒需求量为0.08微克硒/克饮食。当从全血中分离总RNA时，缺硒大鼠的Gpx1 mRNA降至硒充足（0.2微克硒/克饮食）大鼠水平的10%。随着硒的补充，血液Gpx1 mRNA水平呈S形增加至平台期，最低硒需求量为0.08微克硒/克饮食，而谷胱甘肽过氧化物酶-4 mRNA水平不受影响。同样，从分离的红细胞中提取的RNA中的Gpx1 mRNA在缺硒大鼠中降至硒充足水平的23%，最低硒需求量为0.09微克硒/克饮食。进一步的研究表明，全血Gpx1 mRNA主要来源于红细胞，很可能是网织红细胞和年轻红细胞。总之，全血硒蛋白mRNA水平可作为评估硒需求量的分子生物标志物，这表明全血在开发用于营养和医学的分子生物标志物方面具有作为靶组织的潜力。
