Abstract
α-Tocopherolquinone (TQ), a product of α-tocopherol oxidation, can function as an antioxidant after reduction to α-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 (K m = 370 μm;k cat = 5.6 × 103 min −1;k cat/ Km = 15 min−1 · μm −1) 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. TQH2generated 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 α-tocopherol.
Footnotes
- Received March 18, 1997.
- Accepted April 30, 1997.
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Send reprint requests to: Dr. David Siegel, School of Pharmacy C238, UCHSC, 4200 E. 9th Avenue, Denver, CO 80206. E-mail:david.siegel{at}uchsc.edu
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This work was supported by United States Public Health Service Grants CA51210 and CA59585.
- The American Society for Pharmacology and Experimental Therapeutics
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