Abstract
Human placenta thioredoxin reductase (HP-TR) in the presence of NADPH-catalyzed reduction of (15S)-hydroperoxy-(5Z),(8Z),11(Z),13(E)-eicosatetraenoic acid ((15S)-HPETE) into the corresponding alcohol ((15S)-HETE). Incubation of 50 nM HP-TR and 0.5 mM NADPH with 300 microM 15-HPETE for 5 min resulted in formation of 16.5 microM 15-HETE. After 60 min, 74.7 microM 15-HPETE was reduced. The rate of the reduction of 15-HPETE by the HP-TR/NADPH peroxidase system was increased 8-fold by the presence of 2.5 microM selenocystine, a diselenide amino acid. In this case, 15-HPETE was catalytically reduced by the selenol amino acid, selenocysteine, generated from the diselenide by the HP-TR/NADPH system. To a smaller extent, selenodiglutathione or human thioredoxin also potentiated the reduction of 15-HPETE by HP-TR. Hydrogen peroxide and 15-HPETE were reduced at approximately the same rate by HP-TR, thioredoxin, and selenocystine. In contrast, t-butyl hydroperoxide was reduced at a 10-fold lower rate. Our data suggest two novel pathways for the reduction and detoxification of lipid hydroperoxides, hydrogen peroxide, and organic hydroperoxides, i.e. the human thioredoxin reductase-dependent pathway and a coupled reduction in the presence of selenols or selenide resulting from the reduction of selenocystine or selenodiglutathione.
Highlights
From the '![.Medical Nobel Institute for Biochemistry and the §Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden
The aim of the present study was to investigate whether thioredoxin reductase and thioredoxin can reduce lipid hydroperoxides and iflow molecular weight selenium compounds could act as charge transfer catalysts
In order to investigate possible stereospecificity, (15R, S)-HPETE was incubated with CT-thioredoxin reductase (TR)/NADPH and the 15HETE produced (32% reduction) as well as the remaining 15HPETE (68%) were subjected to steric analysis (22)
Summary
Human placenta thioredoxin reductase (HP-TR) in the presence of NADPH-catalyzed reduction of (158)hydroperoxy-(5Z),(8Z),11(Z),13(E)-eicosatetraenoic acid ((158)-HPETE) into the corresponding alcohol ((158)HETE). The rate of the reduction of 15-HPETE by the HP-TWNADPH peroxidase system was increased 8-fold by the presence of 2.5 f.LM selenocystine, a diselenide amino acid. In this case, 15-HPETE was catalytically reduced by the selenol amino acid, selenocysteine, generated from the diselenide by the HP-TR/NADPH system. Our data suggest two novel pathways for the reduction and detoxification of lipid hydroperoxides, hydrogen peroxide, and organic hydroperoxides, i.e. the human thioredoxin reductase-dependent pathway and a coupled reduction in the presence of selenols or selenide resulting from the reduction of selenocystine or selenodiglutathione. Mammalian TR has a broad substrate specificity and reacts with its homologous Trx and with E. coli Trx (11), 5,5' -dithiobis(2-nitrobenzoic acid) (11), GS-Se-SG (12), selenite (13), vitamin K (14), alloxan (15), and the active-site selenocysteine residue in glutathione peroxidases (GSH-Px) (16)
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