The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes

Han, Seung Jin; Kang, Eun Seok; Kim, Hyeong-Jin; Kim, So Hun; Chun, Sang Sik; Ahn, Chul Woo; Soo, Bong; Nam, Moonsuk

doi:10.1016/j.ymgme.2009.01.012

Cited by 28 publications

(21 citation statements)

References 30 publications

(38 reference statements)

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“…Additionally we are able to tease out an apparent "extensive metabolizer" subset of individuals who we know cannot be polymorphic, which probably represents environmental plasticity in NQO1 in this population. Although the effects of NQO1 slow metabolizer polymorphisms/phenotypes have been extensively studied in the context of susceptibility to cancer and effects on drug metabolism, demonstrating environmental mechanisms for enzyme plasticity in human tissues is far more rare (David et al, 2003;Guha et al, 2008;Goodrich et al, 2009;Han et al, 2009;Martin et al, 2009;Vijayakrishnan and Houlston, 2010;Kolesar et al, 2011;Tsvetkov et al, 2011;Li and Zhou, 2014;Lin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In the adult population, increased cardiovascular and cancer risks (Han et al, 2009;Martin et al, 2009;Kolesar et al, 2011;Lin et al, 2014) as well as increasing severity of Alzheimer's disease in the elderly have also been linked to NQO1 polymorphisms (Tsvetkov et al, 2011). Given these associations with childhood diseases and diseases of aging, the NQO1 enzyme is understudied with respect to ontogeny.…”

Section: Introductionmentioning

confidence: 99%

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The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Rougée

Riches

Berman

et al. 2016

Drug Metabolism and Disposition

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The NADPH dehydrogenase quinone oxido-reductase 1 (NQO1) enzyme is an antioxidant and metabolic enzyme that performs two electron reduction of quinones and other chemicals. Based on the physiologic role(s) of NQO1, we hypothesized that expression and activity of this enzyme would vary with age and other demographic variables. Cytosols from 117 archived human livers were investigated for changes in NQO1 with age, sex, obesity, and ethnicity. Protein expression but not activity of NQO1 was weakly negatively correlated with age (Spearman r = -0.2, P = 0.03). No sex differences were observed for either protein expression or activity and for ethnicity; Caucasians had greater NQO1 activity than Asians (P < 0.05). Overweight children had statistically significantly higher NQO1 activity as compared with ideal weight children (P < 0.05) although this difference was not observed in adults. These findings establish that NQO1 is approximately as active in children as adults. However, modeled NQO1 clearance (both allometric and physiologically based pharmacokinetics) predicted maturation at 23 to 26 years. This is almost certainly an overestimate, with error in the model resulting from a small sample size and inability to scale for age-related changes in hepatic cellularity and/or cytosolic protein content, and indicates a delay in reaching maximum clearance through the NQO1 pathway that is affected by physiologic development as much, or more than, biochemical development. Obesity may increase hepatic NQO1 activity in children, which is likely a protective mechanism in oxidative stress, but may also have significant implications for drug and chemical disposition in obese children.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Rougée

Riches

Berman

et al. 2016

Drug Metabolism and Disposition

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“…The enzyme NAD (P)H:quinone acceptor oxidoreductase-1 (NQO1; EC 1.6.99.2) is highly expressed in the vascular wall (Zhu et al, 2007;Han et al, 2009). It plays an important role in the body's defense against oxidative stress in part by detoxifying quinones and their derivatives, thereby preventing their participation in redox cycling (Riley and Workman, 1992;Ross et al, 2000;Han et al, 2009). NQO1 metabolizes thymoquinone, presumably because of its structural similarity to ubiquinone, the natural electron carrier in mitochondria (Sutton et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Endothelium-Dependent Contractions of Isolated Arteries to Thymoquinone Require Biased Activity of Soluble Guanylyl Cyclase with Subsequent Cyclic IMP Production

Detremmerie

Chen

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Preliminary experiments on isolated rat arteries demonstrated that thymoquinone, a compound widely used for its antioxidant properties and believed to facilitate endothelium-dependent relaxations, as a matter of fact caused endothelium-dependent contractions. The present experiments were designed to determine the mechanisms underlying this unexpected response. Isometric tension was measured in rings (with and without endothelium) of rat mesenteric arteries and aortae and of porcine coronary arteries. Precontracted preparations were exposed to increasing concentrations of thymoquinone, which caused concentration-dependent, sustained further increases in tension (augmentations) that were prevented by endothelium removal, Nv-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor], and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; soluble guanylyl cyclase [sGC] inhibitor). In L-NAME-treated rings, the NO-donor diethylenetriamine NONOate restored the thymoquinone-induced augmentations; 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (sGC activator) and cyclic IMP (cIMP) caused similar restorations. By contrast, in ODQ-treated preparations, the cell-permeable cGMP analog did not restore the augmentation by thymoquinone. The compound augmented the content (measured with ultra-high performance liquid chromatography-tandem mass spectrometry) of cIMP, but not that of cGMP; these increases in cIMP content were prevented by endothelium removal, L-NAME, and ODQ. The augmentation of contractions caused by thymoquinone was prevented in porcine arteries, but not in rat arteries, by 1-(5-isoquinolinylsulfonyl)homopiperazine dihydrochloride and trans-4-[(1R)-1-aminoethyl]-N-4-pyridinylcyclohexanecarboxamide dihydrochloride (Rho-kinase inhibitors); in the latter, but not in the former, it was reduced by 3,5-dichloro-N-[[(1a,5a,6-exo,6a)-3-(3,3-dimethylbutyl)-3-azabicyclo[3.1.0]hex-6-yl]methyl]-benzamide hydrochloride (T-type calcium channel inhibitor), demonstrating species/vascular bed differences in the impact of cIMP on calcium handling. Thymoquinone is the first pharmacological agent that causes endothelium-dependent augmentation of contractions of isolated arteries, which requires endothelium-derived NO and biased sGC activation, resulting in the augmented production of cIMP favoring the contractile process.

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“…TaqMan and direct sequencing methods require costly reagents, dedicated instruments, and relatively high level of expertise [20,21]. On the contrary, the proposed method involves a simple PCR step followed by gel electrophoresis.…”

Section: Tri-primer Arms-pcr Analysismentioning

confidence: 99%

Detection of the NQO1 C609T polymorphism by a simple one step Tri-primer Amplification Refractory Mutation System-PCR method

Lajin¹,

Alachkar²

2011

Am. J. Biomed. Sci.

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NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme with antioxidant functions. It catalyzes the two-electron reduction of quinones and nitrogen-oxides, reducing the formation of reactive oxygen species by decreasing one-electron reductions. A common polymorphism in the NQO1 gene involves the substitution of cytosine with thymine (609 C→T), giving rise to a proline to serine substitution, which decreases NQO1 enzymatic activity. The C609T polymorphism was shown to be important in a broad range of biomedical fields, especially cancer research. In this paper, we describe a new method for the detection of C609T based on the Amplification Refractory Mutation System -Polymerase Chain Reaction method (ARMS-PCR). Two specific forward primers differing in length and in the 3′ base, and one common reverse primer were combined in a single PCR reaction. Genotype adscription was based on the amplification of either one or both of two specific amplicons (75 bp for the C allele and 90 bp for the T allele) as shown following agarose gel electrophoresis. The method was validated using a PCR-RFLP method. The proposed method was used to characterize the genotype distribution of the C609T polymorphism in a sample population from Aleppo, Syria, where 2.8% of the sample population were found to be homozygous for the T allele, and 78.8% were found to be homozygous for the C allele.

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The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes

Cited by 28 publications

References 30 publications

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Endothelium-Dependent Contractions of Isolated Arteries to Thymoquinone Require Biased Activity of Soluble Guanylyl Cyclase with Subsequent Cyclic IMP Production

Detection of the NQO1 C609T polymorphism by a simple one step Tri-primer Amplification Refractory Mutation System-PCR method

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