title: Overexpression of thioredoxin reductase 1 inhibits migration of HEK-293 cells.
abstract: BACKGROUND
  TrxR (thioredoxin reductase), in addition to protecting against oxidative stress, plays a role in the redox regulation of intracellular signalling pathways controlling, among others, cell proliferation and apoptosis. The aim of the present study was to determine whether TrxR1 is involved in the regulation of cell migration.
  
  
  RESULTS
  Stably transfected HEK-293 (human embryonic kidney) cells which overexpress cytosolic TrxR1 (HEK-TrxR15 and HEK-TrxR11 cells) were used in the present study. We found that the stimulation of cell motility induced by PKC (protein kinase C) activators, PMA and DPhT (diphenyltin), was inhibited significantly in the HEK-TrxR15 and HEK-TrxR11 cells compared with control cells. The overexpression of TrxR1 also inhibited characteristic morphological changes and reorganization of the F-actin cytoskeleton induced by PMA and DPhT. In addition, the selective activation of PKCdelta by DPhT was inhibited in cells that overexpressed cytosolic TrxR1. Furthermore, rottlerin, a selective inhibitor of PKCdelta, and PKCdelta siRNA (small interfering RNA), suppressed the morphological changes induced by DPhT in the control cells.
  
  
  CONCLUSIONS
  The overexpression of TrxR1 inhibits migration of HEK-293 cells stimulated with PMA and DPhT. Moreover, our observations suggest that this effect is mediated by the inhibition of PKCdelta activation.
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sroka
authors.forename: Agata
authors.initials: A
authors.lastname: Antosik
authors.forename: Jarosław
authors.initials: J
authors.lastname: Czyz
authors.forename: Ivan
authors.initials: I
authors.lastname: Nalvarte
authors.forename: Jerker M
authors.initials: JM
authors.lastname: Olsson
authors.forename: Giannis
authors.initials: G
authors.lastname: Spyrou
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Madeja
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009947:Organotin Compounds / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000378:metabolism; D054481:Thioredoxin Reductase 1 / Q000378:metabolism*; D014162:Transfection
chemical_list: D000199:Actins; D009947:Organotin Compounds; C063612:diphenyltin; D054481:Thioredoxin Reductase 1; D051745:Protein Kinase C-delta