Linked Life Data

11301045

Source:http://linkedlifedata.com/resource/pubmed/id/11301045

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-4-13
pubmed:abstractText
Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III activity and MAT1A expression are compromised under pathological conditions such as alcoholic liver disease and hepatic cirrhosis, and this gene is silenced upon neoplastic transformation of the liver. In the present work, we evaluated whether MAT1A expression could be targeted by the polycyclic arylhydrocarbon (PAH) 3-methylcholanthrene (3-MC) in rat liver and cultured hepatocytes. MAT1A mRNA levels were reduced by 50% following in vivo administration of 3-MC to adult male rats (100 mg/kg, p.o., 4 days' treatment). This effect was reproduced in a time- and dose-dependent fashion in cultured rat hepatocytes, and was accompanied by the induction of cytochrome P450 1A1 gene expression. This action of 3-MC was mimicked by other PAHs such as benzo[a]pyrene and benzo[e]pyrene, but not by the model arylhydrocarbon receptor (AhR) activator 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3-MC inhibited transcription driven by a MAT1A promoter-reporter construct transfected into rat hepatocytes, but MAT1A mRNA stability was not affected. We recently showed that liver MAT1A expression is induced by AdoMet in cultured hepatocytes. Here, we observed that exogenously added AdoMet prevented the negative effects of 3-MC on MAT1A expression. Taken together, our data demonstrate that liver MAT1A gene expression is targeted by PAHs, independently of AhR activation. The effect of AdoMet may be part of the protective action of this molecule in liver damage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1119-28
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11301045-Animals, pubmed-meshheading:11301045-Benz(a)Anthracenes, pubmed-meshheading:11301045-Down-Regulation, pubmed-meshheading:11301045-Drug Interactions, pubmed-meshheading:11301045-Gene Expression, pubmed-meshheading:11301045-Glucocorticoids, pubmed-meshheading:11301045-Hepatocytes, pubmed-meshheading:11301045-Liver, pubmed-meshheading:11301045-Male, pubmed-meshheading:11301045-Methionine Adenosyltransferase, pubmed-meshheading:11301045-Polycyclic Hydrocarbons, Aromatic, pubmed-meshheading:11301045-Protective Agents, pubmed-meshheading:11301045-RNA, Messenger, pubmed-meshheading:11301045-Rats, pubmed-meshheading:11301045-Rats, Wistar, pubmed-meshheading:11301045-Reactive Oxygen Species, pubmed-meshheading:11301045-Receptors, Aryl Hydrocarbon, pubmed-meshheading:11301045-S-Adenosylmethionine
pubmed:year
2001
pubmed:articleTitle
Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine.
pubmed:affiliation
División de Hepatología y Terapia Génica, Facultad de Medicina (Ed. Los Castaños), Universidad de Navarra, C/ Irunlarrea 1, 31008 Pamplona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't