Sodium butyrate inhibits the expression of the human lecithin: cholesterol acyltransferase gene in HepG2 cells by a post-transcriptional mechanism.
We have previously demonstrated that LCAT is downregulated by TGF-beta and that the regulation is post-transcriptional and involves an increased rate of RNA degradation. Sodium butyrate affects the expression of several liver-specific genes including some whose levels are altered during an acute-phase response. We have investigated the effect of sodium butyrate on LCAT activity and mRNA levels in HepG2 cells. Both the LCAT mRNA level and activity were reduced in a dose- and time-dependent manner. The reduction of LCAT mRNA levels was not, however, due to an increased degradation of processed mRNA. The transcriptional activity of the LCAT gene as seen in run-on experiments was not affected by sodium butyrate, whereas the total level of LCAT transcripts was reduced. Thus, LCAT activity and mRNA level in HepG2 cells are decreased by sodium butyrate treatment by a post-transcriptional mechanism, most likely involving increased degradation of pre-mRNA.
Skretting
G
G
Biotechnology Centre of Oslo, University of Oslo, Norway.
Gjernes
E
E
Prydz
H
H
D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D002087:Butyrates; D012333:RNA, Messenger; D020148:Butyric Acid; D007862:Phosphatidylcholine-Sterol O-Acyltransferase