DOI QR코드

DOI QR Code

Iron-fortified recombinant Saccharomyces cerevisiae producing Sus scrofa ferritin heavy-chain recovers iron deficiency in mice

  • Lim, Hwan (College of Veterinary Medicine, Kangwon National University) ;
  • Kim, Jong-Taek (College of Veterinary Medicine, Kangwon National University) ;
  • Kim, Myoung-Dong (Department of Food Science and Biotechnology, Kangwon National University) ;
  • Rhee, Ki-Jong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Jung, Bae Dong (College of Veterinary Medicine, Kangwon National University)
  • Received : 2012.07.04
  • Accepted : 2012.11.16
  • Published : 2012.12.31

Abstract

In this study, we produced iron-fortified yeast (Saccharomyces cerevisiae) producing Sus scrofa ferritin heavy-chain to provide iron supplementation in anemic piglets. We determined whether iron-ferritin accumulated in recombinant yeasts could improve iron deficiency in mice. C57BL/6 male mice exposed to Fe-deficient diet for 2 weeks were given a single dose of ferrous ammonium sulfate (FAS), ferritin-producing recombinant yeast (APO), or APO reacted with iron ($Fe^{2+}$) (FER). The bioavailability of recombinant yeasts was examined by measuring body weight gain, hemoglobin concentration and hematocrit value 1 week later. In addition, ferritin protein levels were evaluated by western blot analysis and iron stores in tissues were measured by inductively coupled plasma spectrometer. We found that anemic mice treated with FER exhibited increased levels of ferritin heavy-chain in spleen and liver. Consistently, this treatment restored the iron concentration in these tissues. In addition, this treatment significantly increased hemoglobin value and the hematocrit ratio. Furthermore, FER treatment significantly enhanced body weight gain. These results suggest that the iron-fortified recombinant yeast strain is bioavailable.

References

  1. Beard JL, Burton JW, Theil EC. Purified ferritin and soybean meal can be sources of iron for treating iron deficiency in rats. J Nutr 1996, 126, 154-160.
  2. Brady PS, Ku PK, Ullrey DE, Miller ER. Evaluation of an amino acid-iron chelate hematinic for the baby pig. J Anim Sci 1978, 47, 1135-1140. https://doi.org/10.2527/jas1978.4751135x
  3. Chang YJ, Jo MY, Hwang EH, Park CU, Kim KS. Recovery from iron deficiency in rats by the intake of recombinant yeast producing human H-ferritin. Nutrition 2005, 21, 520-524. https://doi.org/10.1016/j.nut.2004.07.016
  4. Clark SF. Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol 2009, 25, 122-128. https://doi.org/10.1097/MOG.0b013e32831ef1cd
  5. Collard KJ. Iron homeostasis in the neonate. Pediatrics 2009, 123, 1208-1216. https://doi.org/10.1542/peds.2008-1047
  6. Egeli AK, Framstad T. An evaluation of iron-dextran supplementation in piglets administered by injection on the first, third or fourth day after birth. Res Vet Sci 1999, 66, 179-184. https://doi.org/10.1053/rvsc.1998.0223
  7. Furugouri K, Miyata Y, Shijimaya K, Narasaki N. Developmental changes in serum ferritin of piglets. J Anim Sci 1983, 57, 960-965. https://doi.org/10.2527/jas1983.574960x
  8. Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut 2004, 53, 1190-1197. https://doi.org/10.1136/gut.2003.035758
  9. Gietz GP, Woods RA. Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 2002, 350, 87-96.
  10. Harrison PM, Arosio P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim Biophys Acta 1996, 1275, 161-203. https://doi.org/10.1016/0005-2728(96)00022-9
  11. Jung BD, Shin EJ, Nguyen XK, Jin CH, Bach JH, Park SJ, Nah SY, Wie MB, Bing G, Kim HC. Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration. Neurochem Int 2010, 56, 229-244. https://doi.org/10.1016/j.neuint.2009.10.005
  12. Linder MC, Moor JR, Scott LE, Munro HN. Prenatal and postnatal changes in the content and species of ferritin in rat liver. Biochem J 1972, 129, 455-462. https://doi.org/10.1042/bj1290455
  13. Lipinski P, Starzynski RR, Canonne-Hergaux F, Tudek B, Olinski R, Kowalczyk P, Dziaman T, Thibaudeau O, Gralak MA, Smuda E, Wolinski J, Usinska A, Zabielski R. Benefits and risks of iron supplementation in anemic neonatal pigs. Am J Pathol 2010, 177, 1233-1243. https://doi.org/10.2353/ajpath.2010.091020
  14. May ME, Fish WW. The isolation and properties of porcine ferritin and apoferritin. Arch Biochem Biophys 1977, 182, 396-403. https://doi.org/10.1016/0003-9861(77)90520-3
  15. Murray-Kolb LE, Takaiwa F, Goto F, Yoshihara T, Theil EC, Beard JL. Transgenic rice is a source of iron for iron-depleted rats. J Nutr 2002, 132, 957-960.
  16. Seo HY, Chung YJ, Kim SJ, Park CU, Kim KS. Enhanced expression and functional characterization of the human ferritin H- and L-chain genes in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 2003, 63, 57-63. https://doi.org/10.1007/s00253-003-1350-3
  17. Seo HY, Jeon ES, Chung YJ, Kim KS. Heterologous expression of human ferritin H-chain and L-chain genes in Saccharomyces cerevisiae. KSBB Journal 2002, 17,162-168.
  18. Svoboda M, Drabek J. Iron deficiency in suckling piglets: etiology, clinical aspects and diagnosis. Folia Vet 2005, 49, 104-111.
  19. Theil EC. Ferritin: structure, gene regulation, and cellular function in animals, plants, and microorganisms. Annu Rev Biochem 1987, 56, 289-315. https://doi.org/10.1146/annurev.bi.56.070187.001445