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The Synergistic Effect of Serine with Selenocompounds on the Expression of SelP and GPx in HepG2 Cells

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Abstract

We explored the synergistic effect of serine combined with several selenocompounds or used alone on the expression of selenoprotein P (SelP) and glutathione peroxidase (GPx) in this study. We first compared the SelP and GPx expression difference between HepG2 and Hela cells treated with serine and finally chose HepG2 as experimental cell. In the serine-used-alone experiment, three kinds of selenium nutritional models (low-, adequate-, and high-selenium) were established and serine was 10 times gradient diluted (0.01 to 100 μmol/L). In the combined experiment, the selenocompound doses were set as 0.01, 0.1, and 1 μmol Se/L and serine was set according to its molar ratio with the selenocompounds. We found that SelP and GPx concentrations in the low-, adequate-, and high-selenium models increased following with serine dose. When the concentration of sodium selenite and SeMet was 1 μmol Se/L while MeSeCys was 0.1 and 1 μmol Se/L, SelP concentrations for serine combined with selenocompounds groups were significantly higher than that of selenocompounds used alone. When the concentration of sodium selenite was 0.1 μmol Se/L, SeMet was 0.1 and 1 μmol Se/L while MeSeCys was 0.01 and 1 μmol Se/L, GPx concentrations for serine combined with selenocompounds groups were significantly higher than that of selenocompounds used alone. Our preliminary result indicated the beneficial effect of serine on the expression of SelP and GPx, which suggested that it might be a candidate for combined selenium supplement.

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References

  1. Duntas LH, Benvenga S (2015) Selenium: an element for life. Endocrine 48:756–775

    Article  CAS  PubMed  Google Scholar 

  2. Muth OH, Oldfield JE, Remmert LF, Schubert JR (1958) Effects of selenium and vitamin E on white muscle disease. Science 128:1090

    Article  CAS  PubMed  Google Scholar 

  3. Keshan Disease Research Group of the Chinese Academy of Medical Sciences (1979) Observations on effect of sodium selenite in prevention of Keshan disease. Chin Med J (Engl) 92:471–476

    Google Scholar 

  4. Moreno-Reyes R, Mathieu F, Boelaert M, Begaux F, Suetens C, Rivera MT, Nève J, Perlmutter N, Vanderpas J (2003) Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy. Am J Clin Nutr 78:137–144

    CAS  PubMed  Google Scholar 

  5. Li Q, Zhao ZJ, Yang PZ, Xu XQ, Liu YF, Yu HZ, Ma X, Du R, Zhu L (2015) The prevention effect of selenium on prevalence of children Kashin-Beck disease in active endemic areas in Qinghai plateau. Biol Trace Elem Res. doi:10.1007/s12011-015-0394-4

    Google Scholar 

  6. Alfthan G, Xu GL, Tan WH, Aro A, Wu J, Yang YX, Liang WS, Xue WL, Kong LH (2000) Selenium supplementation of children in a selenium-deficient area in China: blood selenium levels and glutathione peroxidase activities. Biol Trace Elem Res 73:113–125

    Article  CAS  PubMed  Google Scholar 

  7. Değer Y, Mert H, Mert N, Yur F, Kozat S, Yörük IH, Sel T (2008) Serum selenium, vitamin E, and sialic acids concentrations in lambs with white muscle disease. Biol Trace Elem Res 121:39–43

    Article  PubMed  Google Scholar 

  8. Berry MJ, Banu L, Chen YY, Mandel SJ, Kieffer JD, Harney JW, Larsen PR (1991) Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3′ untranslated region. Nature 353:273–276

    Article  CAS  PubMed  Google Scholar 

  9. Wu XQ, Gross HJ (1993) The long extra arms of human tRNA((Ser)Sec) and tRNA(Ser) function as major identify elements for serylation in an orientation-dependent, but not sequence-specific manner. Nucleic Acids Res 21:5589–5594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ohama T, Yang DC, Hatfield DL (1994) Selenocysteine tRNA and serine tRNA are aminoacylated by the same synthetase, but may manifest different identities with respect to the long extra arm. Arch Biochem Biophys 315:293–301

    Article  CAS  PubMed  Google Scholar 

  11. Amberg R, Mizutani T, Wu XQ, Gross HJ (1996) Selenocysteine synthesis in Mammalia: an identity switch from tRNA(Ser) to tRNA(Sec). J Mol Biol 263:8–19

    Article  CAS  PubMed  Google Scholar 

  12. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590

    Article  CAS  PubMed  Google Scholar 

  13. Schweizer U, Streckfuss F, Pelt P, Carlson BA, Hatfield DL, Köhrle J, Schomburg L (2005) Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply. Biochem J 386:221–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Zeng H, Botnen JH, Johnson LK (2008) A selenium-deficient Caco-2 cell model for assessing differential incorporation of chemical or food selenium into glutathione peroxidase. Biol Trace Elem Res 123:98–108

    Article  CAS  PubMed  Google Scholar 

  15. Hollenbach B, Morgenthaler NG, Struck J, Alonso C, Bergmann A, Köhrle J, Schomburg L (2008) New assay for the measurement of selenoprotein P as a sepsis biomarker from serum. J Trace Elem Med Biol 22:24–32

    Article  CAS  PubMed  Google Scholar 

  16. Thiry C, Ruttens A, Pussemier L, Schneider YJ (2013) An in vitro investigation of species-dependent intestinal transport of selenium and the impact of this process on selenium bioavailability. Br J Nutr 109:2126–2134

    Article  CAS  PubMed  Google Scholar 

  17. Hoefig CS, Renko K, Köhrle J, Birringer M, Schomburg L (2011) Comparison of different selenocompounds with respect to nutritional value vs. toxicity using liver cells in culture. J Nutr Biochem 22:945–955

    Article  CAS  PubMed  Google Scholar 

  18. Xia Y, Hill KE, Byrne DW, Xu J, Burk RF (2005) Effectiveness of selenium supplements in a low-selenium area of China. Am J Clin Nutr 81:829–834

    CAS  PubMed  Google Scholar 

  19. Burk RF, Norsworthy BK, Hill KE, Motley AK, Byrne DW (2006) Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial. Cancer Epidemiol Biomarkers Prev 15:804–810

    Article  CAS  PubMed  Google Scholar 

  20. Suzuki KT, Doi C, Suzuki N (2006) Metabolism of 76 Se-methylselenocysteine compared with that of 77 Se-selenomethionine and 82 Se-selenite. Toxicol Appl Pharmacol 217:185–195

    Article  CAS  PubMed  Google Scholar 

  21. Jackson-Rosario SE, Self WT (2010) Targeting selenium metabolism and selenoproteins: novel avenues for drug discovery. Metallomics 2:112–116

    Article  CAS  PubMed  Google Scholar 

  22. Kieliszek M, Błażejak S, Gientka I, Bzducha-Wróbel A (2015) Accumulation and metabolism of selenium by yeast cells. Appl Microbiol Biotechnol 99:5373–5382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Burk RF, Hill KE (2015) Regulation of selenium metabolism and transport. Annu Rev Nutr 35:109–134

    Article  CAS  PubMed  Google Scholar 

  24. Fairweather-Tait SJ, Collings R, Hurst R (2010) Selenium bioavailability: current knowledge and future research requirements. Am J Clin Nutr 91:1484S–1491S

    Article  CAS  PubMed  Google Scholar 

  25. Ning YJ, Wang X, Ren L, Guo X (2013) Effects of dietary factors on selenium levels of children to prevent Kashin-Beck disease during a high-prevalence period in an endemic area: a cohort study. Biol Trace Elem Res 153:58–68

    Article  CAS  PubMed  Google Scholar 

  26. Ning Y, Wang X, Wang S, Zhang F, Zhang L, Lei Y, Guo X (2015) Is it the appropriate time to stop applying selenium enriched salt in Kashin-Beck disease areas in China? Nutrients 7:6195–6212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Miski AM, Kratzer FH (1977) Effects of dietary protein, glycine, and tryptophan on iron metabolism in the growing chick. J Nutr 107:24–34

    CAS  PubMed  Google Scholar 

  28. Greger JL, Snedeker SM (1980) Effect of dietary protein and phosphorus levels on the utilization of zinc, copper and manganese by adult males. J Nutr 110:2243–2253

    CAS  PubMed  Google Scholar 

  29. Bunker VW, Lawson MS, Stansfield MF, Clayton BE (1988) Selenium balance studies in apparently healthy and housebound elderly people eating self-selected diets. Br J Nutr 59:171–180

    Article  CAS  PubMed  Google Scholar 

  30. Nagy G, Benko I, Kiraly G, Voros O, Tanczos B, Sztrik A, Takács T, Pocsi I, Prokisch J, Banfalvi G (2015) Cellular and nephrotoxicity of selenium species. J Trace Elem Med Biol 30:160–170

    Article  CAS  PubMed  Google Scholar 

  31. Brodin O, Eksborg S, Wallenberg M, Asker-Hagelberg C, Larsen EH, Mohlkert D, Lenneby-Helleday C, Jacobsson H, Linder S, Misra S, Björnstedt M (2015) Pharmacokinetics and toxicity of sodium selenite in the treatment of patients with carcinoma in a phase I clinical trial: the SECAR study. Nutrients 7:4978–4994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Misra S, Boylan M, Selvam A, Spallholz JE, Björnstedt M (2015) Redox-active selenium compounds—from toxicity and cell death to cancer treatment. Nutrients 7:3536–3556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Flores Villavicencio LL, Cruz-Jiménez G, Barbosa-Sabanero G, Kornhauser-Araujo C, Mendoza-Garrido ME, de la Rosa G, Sabanero-López M (2014) Human lung cancer cell line A-549 ATCC is differentially affected by supranutritional organic and inorganic selenium. Bioinorg Chem Appl 2014:923834

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wei J, Zeng C, Gong QY, Yang HB, Li XX, Lei GH, Yang TB (2015) The association between dietary selenium intake and diabetes: a cross-sectional study among middle-aged and older adults. Nutr J 14:18

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yuan Z, Xu X, Ye H, Jin L, Zhang X, Zhu Y (2015) High levels of plasma selenium are associated with metabolic syndrome and elevated fasting plasma glucose in a Chinese population: a case-control study. J Trace Elem Med Biol 32:189–194

    Article  CAS  PubMed  Google Scholar 

  36. Shaheen R, Rahbeeni Z, Alhashem A, Faqeih E, Zhao Q, Xiong Y, Almoisheer A, Al-Qattan SM, Almadani HA, Al-Onazi N, Al-Baqawi BS, Saleh MA, Alkuraya FS (2014) Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH. Am J Hum Genet 94:898–904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Acuna-Hidalgo R, Schanze D, Kariminejad A et al (2014) Neu-Laxova syndrome is a heterogeneous metabolic disorder caused by defects in enzymes of the L-serine biosynthesis pathway. Am J Hum Genet 95:285–293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Garofalo K, Penno A, Schmidt BP, Lee HJ, Frosch MP, von Eckardstein A, Brown RH, Hornemann T, Eichler FS (2011) Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest 121:4735–4745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Van Horn MR, Sild M, Ruthazer ES (2013) D-serine as a gliotransmitter and its roles in brain development and disease. Front Cell Neurosci 7:39

    Article  PubMed  PubMed Central  Google Scholar 

  40. Fukada S, Shimada Y, Morita T, Sugiyama K (2006) Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats. Biosci Biotechnol Biochem 70:2403–2409

    Article  CAS  PubMed  Google Scholar 

  41. Liu YQ, Liu Y, Morita T, Sugiyama K (2011) Methionine and serine synergistically suppress hyperhomocysteinemia induced by choline deficiency, but not by guanidinoacetic acid, in rats fed a low casein diet. Biosci Biotechnol Biochem 75:2333–2339

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

All authors read and approved the final manuscript. This study was financially supported by the National Natural Science Foundation of China under the Grant No. 81372989. Q. W. specially thanks Prof. Y. Hu at the Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, for helpful discussions. She also acknowledges hospitality of the staff there during her recent visit to the laboratory.

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Correspondence to Zhen-wu Huang.

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Wang, Q., Sun, Lc., Liu, Yq. et al. The Synergistic Effect of Serine with Selenocompounds on the Expression of SelP and GPx in HepG2 Cells. Biol Trace Elem Res 173, 291–296 (2016). https://doi.org/10.1007/s12011-016-0665-8

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