RGD Reference Report - Acinar distribution of rat liver arylamine N-acetyltransferase: effect of chronic ethanol and endotoxin exposure. - Rat Genome Database

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Acinar distribution of rat liver arylamine N-acetyltransferase: effect of chronic ethanol and endotoxin exposure.

Authors: Pronko, PS  Jarvelainen, HA  Lindros, KO 
Citation: Pronko PS, etal., Pharmacol Toxicol. 2002 Mar;90(3):150-4.
RGD ID: 5131542
Pubmed: PMID:12071337   (View Abstract at PubMed)

The expression of most drug-metabolising enzymes is highest in the perivenous region of the liver, where drug-induced damage is commonly initiated. Arylamine N-acetyltransferase plays an important role in activation or detoxification of many drugs, carcinogens, pesticides and other xenobiotics, but its acinar distribution is unknown. In this study we have analysed the activity of N-acetyltransferase in cell lysates obtained from the periportal or perivenous region by digitonin treatment during in situ liver perfusion. Livers from control animals were compared with rats chronically exposed either to ethanol by liquid diet or to lipopolysaccharide (endotoxin) by intravenous administration. The activity of N-acetyltransferase in the perivenous region was slightly (+ 20%) higher than in the periportal region. Although chronic ethanol exposure did not change total activity, the acinar distribution was reversed to a higher activity in the periportal region. In contrast, chronic endotoxin significantly increased N-acetyltransferase activity, but did not affect the acinar distribution. This increase was counteracted by simultaneous ethanol treatment. N-Acetyltransferase activity in perivenous lysates was significantly reduced after the co-administration of ethanol and endotoxin compared to that after endotoxin alone. Thus, the perivenous zonation of liver N-acetyltransferase is moderate compared to other transferases or P450 isozymes, and the cellular capacity for N-acetylation in the perivenous region, where xenobiotic activation to reactive intermediates dominates, may be insufficient.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nat2Ratresponse to lipopolysaccharide  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nat2  (N-acetyltransferase 2)


Additional Information