Linked Life Data

17560764

Source:http://linkedlifedata.com/resource/pubmed/id/17560764

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2007-11-6
pubmed:abstractText
Primary cultures of epidermal growth factor (EGF)-stimulated hepatocytes are a valuable tool to study the regulation of hepatocyte proliferation. As progression through the cell cycle is generally associated with a reduction in liver-specific functions, we studied the effects of a proliferative response triggered by EGF on the albumin secretion and urea production, and on cytochrome P450 (CYP) 1A1 and CYP2B1 expression and their corresponding 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) activities. It was found that cell cycle entry is associated with decreased albumin secretion and urea production. Furthermore, western blot analysis revealed that in hepatocytes cultured under proliferative conditions, the protein expression of CYP1A1 and CYP2B1 was substantially decreased, as well as the CYP2B-mediated PROD activity. In contrast, EROD activity was not altered. In addition, the expression levels of the liver enriched transcription factors (LETFs) hepatic nuclear factor (HNF) 3beta and HNF4alpha were downregulated under proliferative conditions, whereas the expression of HNF1alpha remained constant. In conclusion, we show that in cultured primary hepatocytes, cell cycle progression significantly modulates albumin secretion, urea production and CYP-mediated biotransformation, probably involving transcriptional regulation by hepatic nuclear factors. Therefore, in order to maintain primary hepatocytes functional in culture, cell cycle inhibition must be achieved.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0887-2333
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1253-7
pubmed:dateRevised
2009-4-10
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Modulation of CYP1A1 and CYP2B1 expression upon cell cycle progression in cultures of primary rat hepatocytes.
pubmed:affiliation
Department of Toxicology, Pharmaceutical Institute, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Tom.Henkens@vub.ac.be
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't