The selenoprotein thioredoxin reductase is expressed in peripheral blood monocytes and THP1 human myeloid leukemia cells – regulation by 1,25‐dihydroxyvitamin D_3 and selenite
Affiliations: Klinische Forschergruppe, Medizinische Poliklinik, Universität Würzburg, Germany | Zentrum Interdisziplinäre Klinische Forschung, Universität Würzburg, Germany | Abteilung für Hämatologie und internistische Onkologie, Universität Regensburg, Germany
Note: [] Address correspondence to: Dr Franz Jakob, Klinische Forschergruppe, Medizinische Poliklinik, Klinikstr. 6‐8, 97070 Würzburg, Germany. Tel.: +49 931 201 7067; Fax: +49 931 201 7068.
Abstract: 1,25(OH)_{2} Vitamin D_{3} (1,25(OH)_{2}D_{3}) and adhesion propagate monocyte differentiation. We identified the selenoprotein thioredoxin reductase (TrxR) as a new molecular target for 1,25(OH)_{2}D_{3} in monocytes during this process. In THP1 monocytic leukemia cells 1,25(OH)_{2}D_{3} stimulated TrxR mRNA levels 2–4‐fold by 4–8 h and enhanced TrxR activity (60%) (as measured by the dithionitrobenzole‐assay) after 24 h, which declined below baseline after 96 h. The addition of 100 nM selenite enhanced (approx. 50%) basal and stimulated enzyme activity in THP1 cells. The relative stimulation by 1,25(OH)_{2}D_{3} was very similar but peak levels were sustained in THP1 cells up to 48 h. Human peripheral blood monocytes (PBM) of different donors showed very low basal TrxR steady state mRNA levels which were markedly enhanced (as analyzed by Northern blotting) after 4 h of adherence to culture dishes. 1,25(OH)_{2}D_{3} (100 nM) further stimulated TrxR mRNA expression (4 h, 3‐fold). TrxR enzyme activity mirrored the mRNA changes. Basal activity was stimulated approx. 25% by adhesion in culture alone and was further stimulated ({\sim}15%) by 1,25(OH)_{2}D_{3} after 4 h. By 24 h similar results were achieved but the effect of 1,25(OH)_{2}D_{3 } could be seen in the presence of 100 nM selenium only. The expression of TrxR and its regulation by 1,25(OH)_{2}D_{3} and selenite in monocytes might be important for their induction of differentiation and maintenance of function.
