SODIUM-BUTYRATE INHIBITS THE EXPRESSION OF THE HUMAN LECITHIN - CHOLESTEROL ACYLTRANSFERASE GENE IN HEPG2 CELLS BY A POSTTRANSCRIPTIONAL MECHANISM

We have previously demonstrated that LCAT is downregulated by TGF-beta and that the regulation is posttranscriptional and involves an increa sed 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 sod ium butyrate on LCAT activity and mRNA levels in HepG2 cells. Both the LCAT mRNA level and activity were reduced in a dose- and time-depende nt manner. The reduction of LCAT mRNA levels was not, however, due to an increased degradation of processed mRNA. The transcriptional activi ty of the LCAT gene as seen in run-on experiments was not affected by sodium butyrate, whereas the total level of LCAT transcripts was reduc ed. Thus, LCAT activity and mRNA level in HepG2 cells are decreased by sodium butyrate treatment by a post-transcriptional mechanism, most l ikely involving increased degradation of pre-mRNA. (C) 1997 Federation of European Biochemical Societies.