Gene expression, 2004-01, Vol.12 (1), p.29-38
2004
Details
- Autor(en) / Beteiligte
- Titel
- Modulation of 3-Hydroxy-3-methylglutaryl-CoA Reductase Gene Expression by CuZn Superoxide Dismutase in Human Fibroblasts and HepG2 Cells
- Ist Teil von
- Gene expression, 2004-01, Vol.12 (1), p.29-38
- Ort / Verlag
- Elmsford, NY: Cognizant Communication Corporation
- Erscheinungsjahr
- 2004
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1052-2166eISSN: 1555-3884DOI: 10.3727/000000004783992198Titel-ID: cdi_proquest_journals_3054972554
- Format
- –
- Schlagworte
- 3-Hydroxy 3-Methylglutaryl-Coa Reductase, Calcium - analysis, Cell Line, Tumor, Cholesterol, Cholesterol - metabolism, Complex systems, Cuzn Superoxide Dismutase, Enzymes, Familial Hypercholesterolemia, Fibroblasts, Fibroblasts - metabolism, Free form, Gene expression, Gene Expression - drug effects, Hepatocellular carcinoma, Hepatocytes, Hepg2 Cells, Homeostasis, Human Fibroblasts, Humans, Hydroxymethylglutaryl CoA Reductases - genetics, Hydroxymethylglutaryl CoA Reductases - metabolism, Hydroxymethylglutaryl-CoA reductase, Hypercholesterolemia, Hypercholesterolemia - drug therapy, Hypercholesterolemia - genetics, Kinases, Lipid metabolism, Low density lipoprotein, Low density lipoprotein receptors, Metabolism, Metabolites, Oxidation, Post-transcription, Reductases, Reverse Transcriptase Polymerase Chain Reaction, Superoxide dismutase, Superoxide Dismutase - pharmacology, Superoxide Dismutase - therapeutic use, Synthesis, Thermal cycling, Variance analysis