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  • Nalvarte, IvanKarolinska Institutet (author)

Overexpression of enzymatically active human cytosolic and mitochondrial thioredoxin reductase in HEK-293 cells : Effect on cell growth and differentiation

  • Article/chapterEnglish2004

Publisher, publication year, extent ...

  • American Society for Biochemistry and Molecular Biology,2004
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-98788
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-98788URI
  • https://doi.org/10.1074/jbc.M408494200DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:1959129URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • The mammalian thioredoxin reductases (TrxR) are selenoproteins containing a catalytically active selenocysteine residue (Sec) and are important enzymes in cellular redox control. The cotranslational incorporation of Sec, necessary for activity, is governed by a stem-loop structure in the 3'-untranslated region of the mRNA and demands adequate selenium availability. The complicated translation machinery required for Sec incorporation is a major obstacle in isolating mammalian cell lines stably overexpressing selenoproteins. In this work we report on the development and characterization of stably transfected human embryonic kidney 293 cells that overexpress enzymatically active selenocysteine-containing cytosolic TrxR1 or mitochondrial TrxR2. We demonstrate that the overexpression of selenium-containing TrxR1 results in lower expression and activity of the endogenous selenoprotein glutathione peroxidase and that the activity of overexpressed TrxRs, rather than the protein amount, can be increased by selenium supplementation in the cell growth media. We also found that the TrxR-overexpressing cells grew slower over a wide range of selenium concentrations, which was an effect apparently not related to increased apoptosis nor to fatally altered intracellular levels of reactive oxygen species. Most surprisingly, the TrxR1- or TrxR2-overexpressing cells also induced novel expression of the epithelial markers CK18, CK-Cam5.2, and BerEP4, suggestive of a stimulation of cellular differentiation.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Damdimopoulos, Anastasios EKarolinska Institutet (author)
  • Nystöm, ChristinaDepartment of Laboratory Medicine, Division of Pathology, F46, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden (author)
  • Nordman, TomasDepartment of Laboratory Medicine, Division of Pathology, F46, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden (author)
  • Miranda-Vizuete, AntonioKarolinska Institutet, Huddinge, Sweden (author)
  • Olsson, Jerker M.Department of Laboratory Medicine, Division of Pathology, F46, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden (author)
  • Eriksson, LennartKarolinska Institutet (author)
  • Björnstedt, MikaelKarolinska Institutet (author)
  • Arnér, Elias S.J.Karolinska Institutet (author)
  • Spyrou, GiannisDepartment of Biosciences at Novum, Center for Biotechnology, Karolinska Institutet, Huddinge, Sweden / Institute of Biomedical Research, Academy of Athens, Greece(Swepub:liu)ioasp42 (author)
  • Karolinska InstitutetDepartment of Laboratory Medicine, Division of Pathology, F46, Karolinska Institutet, Karolinska University Hospital Huddinge, Sweden (creator_code:org_t)

Related titles

  • In:Journal of Biological Chemistry: American Society for Biochemistry and Molecular Biology279:52, s. 54510-545170021-92581083-351X

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