Regulation of rat liver cell 3-hydroxy-3-methylglutaryl coenzyme A reductase by methoxypolyoxyethylated cholesterol

Gregory G. Martin, David J. Shapiro

Research output: Contribution to journalArticlepeer-review

Abstract

A water-soluble derivative of cholesterol, methoxypolyoxyethylated (MPOE) cholesterol, has been synthesized and used to study the regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key regulatory enzyme in cholesterol biosynthesis. MPOE cholesterol causes a specific, rapid and linear decline in HMG-CoA reductase in cultured rat liver cells. MPOE cholesterol is not a direct allosteric inhibitor of HMG-CoA reductase, does not appear to regulate HMG-CoA reductase through changes in membrane environment, and does not change the phosphorylation state and level of activation of rat liver cell HMG-CoA reductase. In order to confirm our data, which were consistent with a model in which MPOE cholesterol regulates the amount of HMG-CoA reductase and not its activity, we made direct measurements of reductase mRNA levels. The decline in HMG-CoA reductase in MPOE cholesterol-treated rat liver cells is preceded by the rapid disappearance of HMG-CoA reductase mRNA. As a water-soluble cholesterol derivative, MPOE cholesterol represents a useful model compound for studies on the regulation of the level of HMG-CoA reductase and its cognate mRNA.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume837
Issue number2
DOIs
StatePublished - Nov 14 1985

Keywords

  • (Rat liver)
  • Cholesterol derivative
  • Enzyme regulation
  • Hydroxymethylglutaryl-CoA reductase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Endocrinology

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