Linked Life Data

8786690

Source:http://linkedlifedata.com/resource/pubmed/id/8786690

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1996-9-20
pubmed:abstractText
We recently suggested that peroxisome proliferators (PP)-induced hepatocyte DNA synthesis may be mediated by a specific peroxisome proliferator activated receptor (PPAR). Heterodimers of the PPAR with the retinoid nuclear receptor, RXR, activate transcription after binding to DR1 response elements of the target genes. DR1 elements are also activated by RXR homodimers formed in the presence of 9-cis retinoic acid (9 cis RA) suggesting that PP and 9 cis RA might regulate an overlapping set of target genes. The present study was therefore designed to test whether 9-cis RA stimulates hepatocyte DNA synthesis. Male Wistar rats were given a single intragastric dose of 9-cis RA (10-100 mg/Kg) or all trans retinoic acid (RA)(200 mg/Kg and 100 mg/Kg), and levels of hepatocyte DNA synthesis after 24 hours were determined by BrdU immunohistochemistry. Effects of 9-cis RA and RA(10(-9)-10(-5)M) on hepatocyte DNA synthesis in primary culture were also examined. Over 10 fold increases in the levels of BrdU incorporation were noted 24 hours after a single dose of 9 cis RA at a dose of 60 and 100 mg/Kg. RA at a dose of 200 mg/Kg induced a 5-6 fold increases in BrdU labeling, while a dose of 100 mg/Kg had no significant effects. Since the RA effect only occurs at higher doses, it may be only after conversion to 9-cis RA. In primary culture of hepatocytes, neither 9-cis RA nor RA with or without EGF had stimulatory effects on hepatocyte DNA synthesis. This is the first report to demonstrate a potent stimulatory effect of 9-cis RA on DNA synthesis of rat hepatocytes in vivo. It is suggested that 9-cis RA exerts this effect through receptor mediated mechanisms similar to PP, both activating genes that regulate hepatocyte proliferation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0024-3205
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
PL211-216
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
9-cis retinoic acid is a direct hepatocyte mitogen in rats.
pubmed:affiliation
Department of Pathology, University of Pittsburgh School of Medicine, PA 15261, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't