Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase gene expression by CuZn superoxide dismutase in human fibroblasts and HepG2 cells

Bruna De Felice, Mariarosaria Santillo, Rosalba Serù, Simona Damiano, Gianfranco Matrone, Robert Roy Wilson, Paolo Mondola

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The homeostasis of intracellular cholesterol in animal cells is highly regulated by a complex system in which the microsomal rate-limiting enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase plays a key role in cholesterol synthesis. Substantial evidence has demonstrated that the cytosolic antioxidant enzyme CuZn superoxide dismutase (SOD1) inhibits the HMG-CoA reductase activity in rat hepatocytes and in human fibroblasts by decreasing cholesterol synthesis. Although these data suggest that SOD1 exerts a physiological role in cholesterol metabolism, it is still unclear whether the decrease of HMG-CoA reductase activity is mediated by transcriptional or by posttranscriptional events. The results of the present study, obtained by one-step RT-PCR assay, demonstrated that both SOD1 and the metal-free form of enzyme (Apo SOD1) inhibit HMG-CoA reductase gene expression in hepatocarcinoma HepG2 cells, in normal human fibroblasts, and in fibroblasts of subjects affected by familiar hypercholesterolemia. Accordingly, SOD1 could be used as a potential agent in the treatment of hypercholesterolemia, even in subjects lacking a functional LDL receptor pathway.

Original languageEnglish (US)
Pages (from-to)29-38
Number of pages10
JournalGene expression
Volume12
Issue number1
DOIs
StatePublished - 2004

Keywords

  • 3-Hydroxy 3-methylglutaryl-CoA reductase
  • Cholesterol
  • CuZn Superoxide dismutase
  • Familial hypercholesterolemia
  • HepG2 cells
  • Human fibroblasts

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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