The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems.

Beyer, Robert E.; Segura‐Aguilar, Juan; Bernardo, Salvatore Di; Cavazzoni, Marika; Fato, Romana; Fiorentini, Diana; Galli, Maria Cristina; Setti, M.; Landi, Laura; Lenaz, Giorgio

doi:10.1073/pnas.93.6.2528

Cited by 280 publications

(158 citation statements)

References 37 publications

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“…NADH-AFR reductase, a trans-oriented activity shows a strong dependency on the CoQ status of the PM, and NQO1 also contribute to the PMRS and are responsive to oxidative stress and aging (29,58). mechanism for reducing PM-associated oxidative stress and, in compensating for mitochondrial dysfunction, as an alternative source of ATP production by increasing NAD levels and glycolysis (28,29). The biochemical characteristics of this system, mainly the dependence on intracellular NADH and CoQ as an electron transfer intermediary, sets it apart from the NOX 1-5 family of enzymes (41).…”

Section: Discussionmentioning

confidence: 99%

“…Cells respond to oxidative stress by transferring electrons from NAD(P)H and ascorbate to extracellular free radicals and/or oxidants (26,27). Coenzyme Q10 (CoQ), a key molecule in the PM redox system (PMRS), can be reduced at the PM by either NAD(P)H-quinone oxidoreductase 1 (NQO1) (28) or NADH-cytochrome b5 reductase (b5R) (29). NQO1 is a NAD(P)H-dependent reductase that is translocated to the inner surface of the PM under stress conditions (30).…”

mentioning

confidence: 99%

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Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

Hyun

Emerson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

249

160

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The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and ␣-tocopherol. Brain aging and neurodegenerative disorders involve impaired energy metabolism and oxidative damage, but the involvement of the PM redox system (PMRS) in these processes is unknown. Caloric restriction (CR), a manipulation that protects the brain against aging and disease, increased activities of PMRS enzymes (NADH-ascorbate free radical reductase, NADH-quinone oxidoreductase 1, NADH-ferrocyanide reductase, NADH-coenzyme Q10 reductase, and NADH-cytochrome c reductase) and antioxidant levels (␣-tocopherol and coenzyme Q10) in brain PM during aging. Age-related increases in PM lipid peroxidation, protein carbonyls, and nitrotyrosine were attenuated by CR, levels of PMRS enzyme activities were higher, and markers of oxidative stress were lower in cultured neuronal cells treated with CR serum compared with those treated with ad libitum serum. These findings suggest important roles for the PMRS in protecting brain cells against age-related increases in oxidative and metabolic stress.Alzheimer's disease ͉ reactive oxygen species ͉ coenzyme Q10 ͉ oxidoreductase

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

Hyun

Emerson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

249

160

View full text Add to dashboard Cite

show abstract

“…Ubiquinol-10 is known to be regenerated from CoQ 10 by electron transport carriers present in various biomembranes and by some enzymes. Plasma membrane DT-diaphorase has recently been proven to maintain CoQ 10 in its reduced antioxidant state as ubiquinol-10 and to protect membrane components from free radical damage such as lipid peroxidation [24].…”

Section: Discussionmentioning

confidence: 99%

The effects of coenzyme Q 10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation

et al. 1998

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“…NQO1 is an obligate two-electron reductase and is classified as a detoxification enzyme primarily because of its ability to reduce quinone substrates directly to their less toxic hydroquinone derivatives bypassing the redox-cycling semiquinone radical (6,7). NQO1 can also function as an antioxidant enzyme reducing ubiquinone and vitamin E quinone to their antioxidant forms (8,9). We have characterized a polymorphism in NQO1 (NQO1*2) (10,11) and demonstrated that individuals homozygous for the NQO1*2 polymorphism (NQO1*2/*2) have no measurable NQO1 activity (12).…”

mentioning

confidence: 99%

Interaction of Human NAD(P)H:Quinone Oxidoreductase 1 (NQO1) with the Tumor Suppressor Protein p53 in Cells and Cell-free Systems

Anwar

Dehn

Siegel

et al. 2003

Journal of Biological Chemistry

123

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NAD(P)H:quinone oxidoreductase 1 (NQO1) has been proposed to stabilize p53 via a redox mechanism involving oxidation of NAD(P)H as a consequence of the catalytic activity of NQO1. We report that treatment of HCT-116 human colon carcinoma cells with the NQO1 inhibitor ES936 had no effect on the levels of p53 protein. ES936 is a mechanism-based inhibitor of NQO1 that irreversibly blocks the catalytic function of the enzyme. This suggests that a redox mechanism involving NQO1-mediated NAD(P)H oxidation is not responsible for the stabilization of p53. We also examined the ability of the NQO1 protein to associate with p53 using co-immunoprecipitation experiments. Results from these experiments demonstrated co-immunoprecipitation of NQO1 with p53 and vice versa. The association between p53 and NQO1 was not affected by treatment of HCT-116 cells with ES936, demonstrating that the association was not dependent on the catalytic activity of NQO1. A comparison of isogenic HCT-116 p53؉/؉ and HCT-116 p53؊/؊ cells demonstrated an interaction of NQO1 and p53 only in the p53؉/؉ cells. Experiments performed in an in vitro transcription/translation system utilizing rabbit reticulocyte lysates confirmed the interaction of NQO1 and p53. In these experiments a full-length p53 coding region was used to express p53 in the presence of recombinant NQO1 protein. An association of p53 and NQO1 was also observed in primary human keratinocytes and mammary epithelial cells. In studies where mdm-2 co-immunoprecipitated with p53, no association of mdm-2 with NQO1 was observed. These data demonstrate an association between p53 and NQO1 that may represent an alternate mechanism of p53 stabilization by NQO1 in a wide variety of human cell types.

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The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems.

Abstract: The experiments reported here were designed to test the hypothesis that the two-electron quinone reductase DT-diaphorase

Cited by 280 publications

References 37 publications

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

The effects of coenzyme Q 10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation

Interaction of Human NAD(P)H:Quinone Oxidoreductase 1 (NQO1) with the Tumor Suppressor Protein p53 in Cells and Cell-free Systems

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