Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2003
Publication Date: 3/17/2003
Citation: Hintze, K.J., Wald, K., Jeffery, E.H., Finley, J.W. 2003. Transcriptional induction of thioredoxin reductase (tr) [abstract]. Journal of Federation of American Societies for Experimental Biology. 17(5):A1371.
Technical Abstract: Previously our lab has demonstrated in-vitro and in-vivo induction of TR activity by sulforaphane (SF) purified from broccoli. Luciferase reporter constructs were built using the TR promoter sequence. TR constructs transfected into HepG2 cells showed a dose dependent increase in transcription when exposed to SF (0.5 to 2 uM; P < 0.0001). The addition of tert-butylhydroquinone to the medium also increased transcription in a dose dependent manner (2.5 to 10 uM; P < 0.0001). Similar patterns were observed for cells transfected with quinone reductase promoter constructs, which are inducible by electrophillic compounds via an antioxidant response element-dependent pathway. In a second experiment, TR construct transfected cells were exposed to SF and/or Se to test whether SF modulates TR transcription with or without Se. The design was a 2X2 factorial: 2.0uM Se + 2.0uM SF, 2.0uM Se, 2.0uM SF, or control media. Combined Se/SF and SF alone both showed a two-fold increase in transcription compared to controls (P < 0.0001), Se had no effect on transcription. However, both Se and SF increased TR activity compared to controls (P < 0.0001) and when combined increased TR activity synergistically (P = 0.036). These data suggest TR is transcriptionally responsive to electrophillic compounds through a mechanism novel from the known Se dependent induction of selenoproteins.