The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells

Biochem Biophys Res Commun. 1995 Mar 8;208(1):405-11. doi: 10.1006/bbrc.1995.1352.

Abstract

In a cultured human hepatoblastoma cell line, Hep G2, chenodeoxycholic acid (CDCA) induced LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold. In contrast, the mRNA levels for mevalonate kinase, farnesyl pyrophosphate synthase and squalene synthase were not changed significantly. The pattern of the induction of the sterol-sensitive genes was similar to the induction by N-acetyl-leucyl-leucyl-norleucinal (ALLN), an SREBP degradation inhibitor, suggesting that CDCA may increase mature SREBPs. CDCA could inhibit the 25-hydroxycholesterol mediated inactivation of SREBP without affecting mRNA levels of SREBPs. These results suggest that CDCA can affect sterol metabolism by a novel mechanism involving the inhibition of the oxysterol-mediated inactivation of SREBP.

Publication types

  • Comparative Study

MeSH terms

  • Alkyl and Aryl Transferases*
  • Base Sequence
  • Cell Line
  • Chenodeoxycholic Acid / pharmacology*
  • Codon
  • DNA-Binding Proteins / metabolism
  • Farnesyl-Diphosphate Farnesyltransferase / biosynthesis
  • Gene Expression / drug effects
  • Geranyltranstransferase
  • Hepatoblastoma
  • Humans
  • Hydroxycholesterols / pharmacology
  • Hydroxymethylglutaryl CoA Reductases / biosynthesis*
  • Hydroxymethylglutaryl-CoA Synthase / biosynthesis*
  • Leupeptins / pharmacology
  • Liver Neoplasms
  • Phosphotransferases (Alcohol Group Acceptor) / biosynthesis
  • Protease Inhibitors / pharmacology
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Receptors, LDL / biosynthesis*
  • Regulatory Sequences, Nucleic Acid
  • Transferases / biosynthesis
  • Tumor Cells, Cultured

Substances

  • Codon
  • DNA-Binding Proteins
  • Hydroxycholesterols
  • Leupeptins
  • Protease Inhibitors
  • RNA, Messenger
  • Receptors, LDL
  • Chenodeoxycholic Acid
  • acetylleucyl-leucyl-norleucinal
  • 25-hydroxycholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Transferases
  • Hydroxymethylglutaryl-CoA Synthase
  • Alkyl and Aryl Transferases
  • Geranyltranstransferase
  • Farnesyl-Diphosphate Farnesyltransferase
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase