Linked Life Data

7746280

Source:http://linkedlifedata.com/resource/pubmed/id/7746280

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-6-12
pubmed:abstractText
NAD(P):quinone acceptor oxidoreductase (quinone reductase) (DT-diaphorase, EC 1.6.99.2) is involved in the process of reductive activation of cytotoxic antitumor quinones and nitrobenzenes. In this study, we initially examined the relative abilities of mouse, rat, and human quinone reductases to reduce two prodrugs, CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] and EO9 [5-(1-aziridinyl)-3-(hydroxymethyl)-2-(3-hydroxy-1-propenyl)-1- methyl-1H-indole-4,7-dione]. By using Escherichia coli-expressed quinone reductases and evaluating them under identical conditions, we confirmed previous finding showing that the human enzyme is not as effective as the rat enzyme in reducing CB 1954 and EO9, although the two enzymes have similar NAD(P)H-menadione reductase activities. Interestingly, although the amino acid sequence of mouse quinone reductase is more homologous to that of the rat enzyme, we found that the mouse enzyme behaves similarly to the human enzyme in its ability to reduce these compounds and to generate drug-induced DNA damage. To determine the region of quinone reductase that is responsible for the catalytic differences, two mouse-rat chimeric enzymes were generated. MR-P, a chimeric enzyme that has mouse amino-terminal and rat carboxy-terminal segments of quinone reductase, was shown to have catalytic properties resembling those of rat quinone reductase, and RM-P, a chimeric enzyme that has rat amino-terminal and mouse carboxyl-terminal segments of quinone reductase, was shown to have catalytic properties resembling those of mouse quinone reductase. In addition, MR-P and RM-P were found to be inhibited by flavones with Ki values similar to those for rat and mouse quinone reductases, respectively. Based on these results, we propose that the carboxyl-terminal portion of the enzyme plays an important role in the reduction of cytotoxic drugs and the binding of flavones.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
934-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7746280-Amino Acid Sequence, pubmed-meshheading:7746280-Animals, pubmed-meshheading:7746280-Aziridines, pubmed-meshheading:7746280-Base Sequence, pubmed-meshheading:7746280-DNA Damage, pubmed-meshheading:7746280-DNA Primers, pubmed-meshheading:7746280-Escherichia coli, pubmed-meshheading:7746280-Humans, pubmed-meshheading:7746280-Indolequinones, pubmed-meshheading:7746280-Indoles, pubmed-meshheading:7746280-Kinetics, pubmed-meshheading:7746280-Mice, pubmed-meshheading:7746280-Molecular Sequence Data, pubmed-meshheading:7746280-NAD(P)H Dehydrogenase (Quinone), pubmed-meshheading:7746280-Prodrugs, pubmed-meshheading:7746280-Rats, pubmed-meshheading:7746280-Recombinant Fusion Proteins, pubmed-meshheading:7746280-Sequence Homology, Amino Acid, pubmed-meshheading:7746280-Species Specificity
pubmed:year
1995
pubmed:articleTitle
Catalytic properties of NAD(P)H:quinone acceptor oxidoreductase: study involving mouse, rat, human, and mouse-rat chimeric enzymes.
pubmed:affiliation
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't