Overexpression of thioredoxin reductase 1 inhibits migration of HEK-293 cells.
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.
Sroka
Jolanta
J
Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
Antosik
Agata
A
Czyz
Jarosław
J
Nalvarte
Ivan
I
Olsson
Jerker M
JM
Spyrou
Giannis
G
Madeja
Zbigniew
Z
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
D000199:Actins; D009947:Organotin Compounds; C063612:diphenyltin; D054481:Thioredoxin Reductase 1; D051745:Protein Kinase C-delta