Linked Life Data

9679543

Source:http://linkedlifedata.com/resource/pubmed/id/9679543

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1998-8-10
pubmed:abstractText
The rat can be protected against aflatoxin B1 (AFB1) hepatocarcinogenesis by being fed on a diet containing the synthetic antioxidant ethoxyquin. Evidence suggests that chemoprotection against AFB1 is due to increased detoxification of the mycotoxin by one or more inducible drug-metabolising enzymes. The glutathione S-transferase (GST) isoenzymes in rat liver that contribute to ethoxyquin-induced chemoprotection against AFB1 have been identified by protein purification. This approach resulted in the isolation of several heterodimeric class alpha GST, all of which contained the A5 subunit and possessed at least 50-fold greater activity towards AFB1-8,9-epoxide than previously studied transferases. Molecular cloning and heterologous expression of rat GSTA5-5 has led to the demonstration that it exhibits substantially greater activity for AFB1-8,9-epoxide than other rat transferases. The A5 homodimer can also catalyse the conjugation of glutathione with other epoxides, such as trans-stilbene oxide and 1,2-epoxy-3-(4'-nitrophenoxy)propane, and possesses high catalytic activity for the reactive aldehyde 4-hydroxynonenal. Western blotting has shown that the A5 subunit is not only induced by ethoxyquin but that it is also induced by other cancer chemopreventive agents, such as butylated hydroxyanisole, oltipraz, benzyl isothiocyanate, indole-3-carbinol and coumarin. In addition to GSTA5, we have identified a novel aflatoxin-aldehyde reductase (AFAR) that is similarly induced by ethoxyquin. However, immunoblotting has shown that GSTA5 and AFAR are not always co-ordinately regulated by chemoprotectors. In order to gain a better understanding of the mechanisms responsible for the induction of GSTA5 protein, the GSTA5 gene has been cloned. It was isolated on two overlapping bacteriophage lambda clones and found to be approximately 12 kb in length. The transcriptional start site of GSTA5 has been identified 228 bp upstream from the ATG translational initiation codon. Computer-assisted analysis of the upstream sequence has indicated the presence of a putative antioxidant responsive element (located between -421 and -429 bp) which may be responsible for the induction of GSTA5 by chemopreventive agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0009-2797
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
111-112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-67
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9679543-Aflatoxin B1, pubmed-meshheading:9679543-Aldehyde Reductase, pubmed-meshheading:9679543-Amino Acid Sequence, pubmed-meshheading:9679543-Animals, pubmed-meshheading:9679543-Antioxidants, pubmed-meshheading:9679543-Base Sequence, pubmed-meshheading:9679543-Biotransformation, pubmed-meshheading:9679543-Cloning, Molecular, pubmed-meshheading:9679543-DNA, pubmed-meshheading:9679543-Drug Resistance, pubmed-meshheading:9679543-Enzyme Induction, pubmed-meshheading:9679543-Ethoxyquin, pubmed-meshheading:9679543-Glutathione Transferase, pubmed-meshheading:9679543-Liver Neoplasms, Experimental, pubmed-meshheading:9679543-Metabolic Detoxication, Drug, pubmed-meshheading:9679543-Molecular Sequence Data, pubmed-meshheading:9679543-Oxidative Stress, pubmed-meshheading:9679543-Protein Conformation, pubmed-meshheading:9679543-Rats
pubmed:year
1998
pubmed:articleTitle
Regulation of rat glutathione S-transferase A5 by cancer chemopreventive agents: mechanisms of inducible resistance to aflatoxin B1.
pubmed:affiliation
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't