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-Tocopherolquinone by Human NAD(P)H:Quinone
Oxidoreductase: The Role of -Tocopherolhydroquinone as a
Cellular Antioxidant
Department of Pharmaceutical Sciences, School of Pharmacy and
Cancer Center, University of Colorado Health Sciences Center, Denver,
Colorado 80262 (D.S., E.M.B., D.R.), and
Department of Pharmacology and
Toxicology, College of Pharmacy and Cancer Center, University of
Arizona, Tucson, Arizona 85721 (J.A.B., D.C.L.)
-Tocopherolquinone (TQ), a product of -tocopherol oxidation, can
function as an antioxidant after reduction to
-tocopherolhydroquinone (TQH2). We examined the ability
of human NAD(P)H:quinone oxidoreductase (NQO1) to catalyze the
reduction of TQ to TQH2 in cell-free and cellular systems.
In reactions with purified human NQO1, TQ was reduced to
TQH2. Kinetic parameters for the reduction of TQ by NQO1
(Km = 370 µM;
kcat = 5.6 × 103
min
1;
kcat/Km = 15 min1 · µM1) indicate that
NQO1 can efficiently reduce TQ to TQH2. A comparison of the
rate of reduction of TQ and coenzyme Q10 by NQO1
showed that TQ is reduced more efficiently than coenzyme
Q10. Experiments with either Chinese hamster ovary
(CHO) cells stably transfected with human NQO1 or CHO cell sonicates
demonstrated a correlation between NQO1 activity and TQ reduction to
TQH2. CHO cells with elevated NQO1 generated and
maintained higher levels of TQH2 after treatment
with TQ relative to NQO1-deficient CHO cells. TQH2
generated from NQO1-mediated reduction of TQ prevented cumene
hydroperoxide-induced lipid peroxidation in rat liver microsomes. In
addition, cumene hydroperoxide-induced lipid peroxidation was inhibited
more efficiently by TQ in CHO cell lines with elevated NQO1 activity.
These data demonstrate that NQO1 can reduce TQ to
TQH2 and that TQH2 can function
as an efficient antioxidant. This work suggests that one of the
physiological functions of NQO1 may be to regenerate antioxidant forms
of -tocopherol.
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