Linked Life Data

16757079

Source:http://linkedlifedata.com/resource/pubmed/id/16757079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-7-10
pubmed:abstractText
Rat liver glutathione-S-transferase Pi-(GST-P)-positive enzyme-altered foci (EAF) are preneoplastic lesions that develop in response to carcinogenic stress. They are often used as endpoints in e.g. chemopreventive studies. In this study we characterize a pAkt-negative/ceramide-positive (pAkt-/cer+) EAF phenotype, as defined by immunohistochemistry for pAkt and ceramide species, in diethylnitrosamine(DEN)-, phenobarbital- or aflatoxinB1-treated rats. There was a close to 100% overlap for the pAkt and the ceramide marker. Furthermore, serial sections stained for PTEN indicated a close correlation between PTEN-positive and pAkt-negative lesions in DEN-treated rats. Experiments with DEN-treated rats given sphingomyelin in the diet suggested that sphingomyelin selectively targeted these lesions. In in vitro experiments sphingosine rapidly decreased pAkt levels in hepatocytes, and in experiments with hepatocytes from DEN-treated rats sphingosine selectively killed EAF cells. Furthermore, pretreatment with antisense Akt oligonucleotides in vitro sensitized non-EAF hepatocytes, so that EAF and non-EAF cells became equally sensitive to sphingosine. It is concluded that rat liver, in response to carcinogenic stress, develops a distinct EAF phenotype exhibiting low pAkt levels and concomitant alterations in sphingolipid metabolism. Our data also suggest that pAkt-/cer+ EAF are selectively targeted by sphingolipids in the diet and that lesions with this phenotype should be of particular interest for future studies on chemopreventive effects that may affect sphingolipid metabolism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0278-6915
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1552-61
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16757079-Animals, pubmed-meshheading:16757079-Cell Survival, pubmed-meshheading:16757079-Cells, Cultured, pubmed-meshheading:16757079-Ceramides, pubmed-meshheading:16757079-Diet, pubmed-meshheading:16757079-Drug Combinations, pubmed-meshheading:16757079-Female, pubmed-meshheading:16757079-Glutathione Transferase, pubmed-meshheading:16757079-Hepatocytes, pubmed-meshheading:16757079-Liver, pubmed-meshheading:16757079-Liver Neoplasms, Experimental, pubmed-meshheading:16757079-Oligonucleotides, Antisense, pubmed-meshheading:16757079-PTEN Phosphohydrolase, pubmed-meshheading:16757079-Precancerous Conditions, pubmed-meshheading:16757079-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16757079-Rats, pubmed-meshheading:16757079-Rats, Sprague-Dawley, pubmed-meshheading:16757079-Sphingomyelins, pubmed-meshheading:16757079-Sphingosine
pubmed:year
2006
pubmed:articleTitle
Dietary sphingolipids suppress a subset of preneoplastic rat liver lesions exhibiting high PTEN, low phospho-Akt and high levels of ceramide species.
pubmed:affiliation
Occupational Toxicology Group, Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-171 77 Stockholm, Sweden.
pubmed:publicationType
Journal Article