Blood glutathione peroxidase-1 mRNA levels can be used as molecular biomarkers to determine dietary selenium requirements in rats.
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.
Department of Nutritional Sciences, University of Wisconsin, 1415 Linden Drive, Madison, WI 53706, USA. sunde@nutrisci.wisc.edu
Roger A
RA
Sunde
Kevin M
KM
Thompson
Jacqueline K
JK
Evenson
Britta M
BM
Thompson
D000818:Animals; D015415:Biomarkers / Q000097:blood; D005591:Chemical Fractionation; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000097:blood* / Q000235:genetics*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D023282:Nuclease Protection Assays; D009751:Nutritional Requirements; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D051381:Rats; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D051140:Selenoproteins / Q000097:blood / Q000235:genetics; D000094765:Glutathione Peroxidase GPX1
D015415:Biomarkers; D012333:RNA, Messenger; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat