Mode of Action of Peroxisome Proliferators as Hypolipidemic Drugs
| Autor: | Jacob Bar-Tana, Rachel Hertz, Janette Bishara-Shieban |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
chemistry.chemical_classification
medicine.medical_specialty Apolipoprotein B medicine.drug_class Catabolism Apolipoprotein C-III Peroxisome proliferator-activated receptor Cell Biology Fibrate Biology Peroxisome Biochemistry Endocrinology chemistry Hepatocyte nuclear factor 4 Internal medicine medicine biology.protein lipids (amino acids peptides and proteins) Receptor Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 270:13470-13475 |
| ISSN: | 0021-9258 8491-8497 |
| Popis: | The hypolipidemic effect exerted by beta,beta'-tetramethyl-hexadecanedioic acid (Medica 16) is accounted for by enhanced catabolism of plasma triglyceride-rich lipoproteins due to a decrease in plasma apolipoprotein C-III (Frenkel, B., Mayorek, N., Hertz, R., and Bar-Tana, J. (1988) J. Biol. Chem. 263, 8491-8497; Frenkel, B., Bishara-Shieban, J., and Bar-Tana, J. (1994) Biochem. J. 298, 409-414). Decrease in apolipoprotein C-III exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates (e.g. Medica 16, fibrate drugs) is shown here to result from suppression of apolipoprotein C-III gene expression. Transcriptional suppression of apolipoprotein C-III is due to transcriptional suppression of hepatic nuclear factor (HNF)-4 as well as displacement of HNF-4 from the apolipoprotein C-III promoter. HNF-4 displacement exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates is mediated by the peroxisome proliferators activated receptor (PPAR). Transcriptional suppression of HNF-4-enhanced genes (e.g. apolipoprotein C-III) along with transcriptional activation of peroxisomal and other genes by hypolipidemic drugs may account for their broad spectrum pharmacological effect. |
| Databáze: | OpenAIRE |
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