title: Association between plasma selenium level and NRF2 target genes expression in humans.
abstract: Animal studies in rodent and in vitro studies indicate compensatory role of nuclear factor (erythroid-derived 2)-like (Nrf2) and Nrf2-regulated antioxidant and phase II biotransformation enzymes for the dietary selenium (Se) deficiency or for the loss of selenoproteins. To explore associations between plasma Se level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 96 healthy non-smoking men living in Central Poland aged 18-83 years with relatively low plasma Se level. NRF2, KEAP2, CAT, EPHX1, GCLC, GCLM, GPX2, GSR, GSTA1, GSTM1, GSTP1, GSTT1, HMOX1, NQO1, PRDX1, SOD1, SOD2, TXNRD1 transcript levels in peripheral blood leukocytes and polymorphism of NRF2-617C/A (rs6721961) in blood genomic DNA were determined by means of quantitative real-time PCR. Mean plasma Se level was found to be 51.10±15.25μg/L (range 23.86-96.18μg/L). NRF2 mRNA level was positively correlated with expression of investigated NRF2-target genes. The multivariate linear regression adjusting for selenium status showed that plasma Se level was significantly inversely associated only with expression of GSTP1 (β-coef.=-0.270, p=0.009), PRDXR1 (β-coef.=-0.245, p=0.017) and SOD2 with an inverse trend toward signiﬁcance (β-coef.=-0.186, p=0.074), but without an effect of NRF2 gene variants. NRF2 expression was inversely associated with age (r=-0.23, p=0.03) and body mass index (r=-0.29, p<0.001). The findings may suggest a possible link between plasma Se level and cytoprotective response at gene level in humans.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy Street, 91-348 Lodz, Poland. Electronic address: edyta@imp.lodz.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Reszka
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy Street, 91-348 Lodz, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Wieczorek
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy Street, 91-348 Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jablonska
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy Street, 91-348 Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Janasik
authors.affiliation: Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 36/50 Sporna Street, 91-738 Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Fendler
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Teresy Street, 91-348 Lodz, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Wasowicz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005786:Gene Expression Regulation; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012643:Selenium / Q000097:blood*; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D012643:Selenium
keywords: Cytoprotective genes; Gene expression; Human circulating leukocytes; NRF2; Selenium