Isolation of DT-Diaphorase [NAD(P)H Dehydrogenase (Quinone)] from Rat Liver Cytosol: Identification of New Enzyme Substrates, Carcinogenic Aristolochic Acids

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Title:Isolation of DT-Diaphorase [NAD(P)H Dehydrogenase (Quinone)] from Rat Liver Cytosol: Identification of New Enzyme Substrates, Carcinogenic Aristolochic Acids
Creators:
Stiborová, Marie
Hájek, Miroslav
Vošmiková, Hana
Frei, Eva
Schmeiser, Heinz H.
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 66, 6, pp. 959-972
Uncontrolled Keywords:Drugs, Enzymes, NAD(P)H dehydrogenase (quinone), Chinese herbs nephropathy, Inducers, DT-Diaphorase, Oxidases, Reductive activation, Carcinogens, Purification procedure, Carcinogenesis, Aristolochic acids

Abstract

Cytosolic fractions isolated from liver and kidney of rats treated with β-naphthoflavone, Sudan I, ellipticine, phenobarbital, ethanol, acetone and natural carcinogenic and nephrotoxic nitroaromatics, aristolochic acids, were tested for the activity of DT-diaphorase [NAD(P)H dehydrogenase (quinone), EC 1.6.99.2]. While the most efficient inducers of DT-diaphorase in liver were Sudan I, ellipticine and aristolochic acids, the highest increase in the DT-diaphorase activity in kidney was produced by aristolochic acids. No increase in the enzyme activity was determined after treatment of rats with acetone. DT-Diaphorase was isolated from liver cytosol of Sudan I-treated rats by the procedure consisting of fractionation with ammonium sulfate, gel permeation chromatography on a Sephadex G-150 column, affinity chromatography on an Affi-Gel Blue (Cibracron Blue Agarose) column and re-chromatography on Sephadex G-150. Rat DT-diaphorase catalyzed NAD(P)H-dependent reduction of menadione (vitamin K<sub>3</sub>), vitamin K<sub>1</sub> and 4-nitrosophenol as substrates. Moreover, we newly identified two carcinogenic nitroaromatic compounds, aristolochic acids, as other substrates of DT-diaphorase. A selective inhibitor of the human DT-diaphorase, dicoumarol, inhibited the catalytic activity of the rat purified enzyme. <p>

Title:Isolation of DT-Diaphorase [NAD(P)H Dehydrogenase (Quinone)] from Rat Liver Cytosol: Identification of New Enzyme Substrates, Carcinogenic Aristolochic Acids
Creators:
Stiborová, Marie
Hájek, Miroslav
Vošmiková, Hana
Frei, Eva
Schmeiser, Heinz H.
Uncontrolled Keywords:Drugs, Enzymes, NAD(P)H dehydrogenase (quinone), Chinese herbs nephropathy, Inducers, DT-Diaphorase, Oxidases, Reductive activation, Carcinogens, Purification procedure, Carcinogenesis, Aristolochic acids
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:66
Number:6
Page Range:pp. 959-972
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc20010959UNSPECIFIED
ID Code:1835
Item Type:Article
Deposited On:06 Feb 2009 17:13
Last Modified:06 Feb 2009 16:13

Citation

Stiborová, Marie; Hájek, Miroslav; Vošmiková, Hana; Frei, Eva; Schmeiser, Heinz H. (2001) Isolation of DT-Diaphorase [NAD(P)H Dehydrogenase (Quinone)] from Rat Liver Cytosol: Identification of New Enzyme Substrates, Carcinogenic Aristolochic Acids. Collection of Czechoslovak Chemical Communications, 66 (6). pp. 959-972. ISSN 0010-0765

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