DT-Diaphorase Maintains the Reduced State of Ubiquinones in Lipid Vesicles thereby Promoting their Antioxidant Function

Landi, Laura; Fiorentini, Diana; Galli, Maria Cristina; Segura‐Aguilar, Juan; Beyer, Robert E.

doi:10.1016/s0891-5849(96)00294-8

Cited by 94 publications

(43 citation statements)

References 29 publications

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“…Lipid peroxidation leads to a decrease in coenzyme Q 10 content and inactivation of respiratory chain enzymes, whereas administration of coenzyme Q 10 preserves mitochondrial respiratory function in aged rat skeletal muscle (5,21). NADPH:quinone oxidoreductase maintains coenzyme Q 10 in a reduced state, promoting its antioxidant function (22). Administration of coenzyme Q 10 increases the activity of the electron transport chain both in vitro and in vivo and protects against ischemia͞reperfusion damage in the heart (23-28) and against damage produced by adriamycin in perfused rat livers (29).…”

Section: Resultsmentioning

confidence: 99%

Coenzyme Q ₁₀ administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Matthews

Yang

Browne

et al. 1998

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

523

339

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Coenzyme Q 10 is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q 10 increased cerebral cortex concentrations in 12-and 24-month-old rats. In 12-month-old rats administration of coenzyme Q 10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q 10 . Oral administration of coenzyme Q 10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. These results show that oral administration of coenzyme Q 10 increases both brain and brain mitochondrial concentrations. They provide further evidence that coenzyme Q 10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.Coenzyme Q is an essential cofactor in the electron transport chain where it accepts electrons from complex I and II (1-3). Coenzyme Q also serves as an important antioxidant in both mitochondria and lipid membranes (4, 5). Coenzyme Q, which also is known as ubiquinone, is a lipid-soluble compound composed of a redox active quinoid moiety and a hydrophobic ''tail.'' The predominant form of coenzyme Q in humans is coenzyme Q 10 , which contains 10 isoprenoid units in the tail, whereas the predominant form in rodents is coenzyme Q 9 , which has nine isoprenoid units in the tail. Coenzyme Q is soluble and mobile in the hydrophobic core of the phospholipid bilayer of the inner membrane of the mitochondria where it transfers electrons one at a time to complex III of the electron transport chain.There has been considerable interest in the use of coenzyme Q 10 for the treatment of mitochondrial disorders. Several reports found both clinical and biochemical improvement in patients with mitochondrial disorders (6-10). If defects in energy metabolism and oxidative damage play a role in the pathogenesis of neurodegenerative diseases (11, 12), then treatment with coenzyme Q 10 could exert beneficial therapeutic effects. We previously showed that oral administration of coenzyme Q 10 significantly attenuated lesions produced by intrastriatal administration of malonate in rats, as well as malonate-induced depletions of ATP and increases in lactate concentrations (13). In the present study, we examined the effects of oral administration of coenzyme Q 10 on brain and brain mitochondrial concentrations. We examined both oxidized and reduced coenzyme Q 10 levels because the latter is the form that exerts antioxidant effects (4, 5). We examined neuroprotective effects against striatal lesions produced by systemic administration of 3-nitropropionic acid (3-NP) and survival in a transgenic animal model of familial amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODSStudies of coenzyme Q 10 were carried out in male SpragueDawley rats. Coenzyme Q 10 powder (Vitaline Formulas, Ashland, OR) was formulated in rat chow (Agw...

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Section: Resultsmentioning

confidence: 99%

Coenzyme Q ₁₀ administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Matthews

Yang

Browne

et al. 1998

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

523

339

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“…Given that chromium in nature exists primarily as chromite ore (FeCr 2 O 4 ), in which it is present in the 3ϩ state (2), and that the introduction of chromate in the environment is a relatively recent event, this is unlikely. Instead, our ongoing work strongly suggests that ChrR and YieF may be bacterial counterparts of the mammalian DT-diaphorase (7,15,17) with the main biological role of detoxifying quinonoid compounds, which are a constant threat to bacteria (37). Their protection against chromate toxicity may be a reflection of a more generalized role of divalent reduction of electrophiles that are prone to one-electron reduction and ROS generation.…”

Section: Discussionmentioning

confidence: 99%

Chromate-Reducing Properties of Soluble Flavoproteins from Pseudomonas putida and Escherichia coli

Ackerley

González

Park

et al. 2004

Appl Environ Microbiol

267

208

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Cr(VI) (chromate) is a toxic, soluble environmental contaminant. Bacteria can reduce chromate to the insoluble and less toxic Cr(III), and thus chromate bioremediation is of interest. Genetic and protein engineering of suitable enzymes can improve bacterial bioremediation. Many bacterial enzymes catalyze oneelectron reduction of chromate, generating Cr(V), which redox cycles, generating excessive reactive oxygen species (ROS). Such enzymes are not appropriate for bioremediation, as they harm the bacteria and their primary end product is not Cr(III). In this work, the chromate reductase activities of two electrophoretically pure soluble bacterial flavoproteins-ChrR (from Pseudomonas putida) and YieF (from Escherichia coli)-were examined. Both are dimers and reduce chromate efficiently to Cr(III) (k cat /K m ‫؍‬ ϳ2 ؋ 10 4 M ؊1 ⅐ s ؊1 ). The ChrR dimer generated a flavin semiquinone during chromate reduction and transferred >25% of the NADH electrons to ROS. However, the semiquinone was formed transiently and ROS diminished with time. Thus, ChrR probably generates Cr(V), but only transiently. Studies with mutants showed that ChrR protects against chromate toxicity; this is possibly because it preempts chromate reduction by the cellular one-electron reducers, thereby minimizing ROS generation. ChrR is thus a suitable enzyme for further studies. During chromate reduction by YieF, no flavin semiquinone was generated and only 25% of the NADH electrons were transferred to ROS. The YieF dimer may therefore be an obligatory four-electron chromate reducer which in one step transfers three electrons to chromate and one to molecular oxygen. As a mutant lacking this enzyme could not be obtained, the role of YieF in chromate protection could not be directly explored. The results nevertheless suggest that YieF may be an even more suitable candidate for further studies than ChrR.

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“…The results of earlier studies have established that AAPH leads to the formation of carboncentered radicals, which yield alklyperoxyl radicals and hydroperoxides that are capable of modifying lipid and DNA under aerobic conditions (13)(14)(15)(16). In order to study the effect of hSelM overexpression under high levels of free radicals, the concentration of total antioxidant and H 2 O 2 was determined in the serum of CMV/GFP-hSelM Tg and non-Tg rats after AAPH injection using an ELISA kit.…”

Section: Effect Of Selm Overexpression On the H 2 O 2 And Total Antiomentioning

confidence: 99%

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang¹,

Sin²,

Kim³

et al. 2008

Int J Mol Med

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Abstract. Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H 2 O 2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.

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DT-Diaphorase Maintains the Reduced State of Ubiquinones in Lipid Vesicles thereby Promoting their Antioxidant Function

Cited by 94 publications

References 29 publications

Coenzyme Q ₁₀ administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Coenzyme Q ₁₀ administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Chromate-Reducing Properties of Soluble Flavoproteins from Pseudomonas putida and Escherichia coli

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

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DT-Diaphorase Maintains the Reduced State of Ubiquinones in Lipid Vesicles thereby Promoting their Antioxidant Function

Cited by 94 publications

References 29 publications

Coenzyme Q 10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Coenzyme Q 10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Chromate-Reducing Properties of Soluble Flavoproteins from Pseudomonas putida and Escherichia coli

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

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Coenzyme Q ₁₀ administration increases brain mitochondrial concentrations and exerts neuroprotective effects

Coenzyme Q ₁₀ administration increases brain mitochondrial concentrations and exerts neuroprotective effects