PPAR gamma ligand troglitazone lowers cholesterol synthesis in HepG2 and Caco-2 cells via a reduced concentration of nuclear SREBP-2.
Exp Biol Med (Maywood)
; 231(8): 1365-72, 2006 Sep.
Article
en En
| MEDLINE
| ID: mdl-16946405
Cholesterol synthesis in animal cells is regulated by sterol regulatory element-binding protein (SREBP)-2. The objective of this study was to investigate whether activation of peroxisome proliferator-activatedreceptor (PPAR)-gamma influences the SREBP-2 dependent cholesterol synthesis in liver and intestinal cells. Therefore, HepG2 and Caco-2 cells were incubated with and without 10 or 30 microM of troglitazone, a synthetic PPAR gamma agonist, for 4 hrs. Incubation with 10 or 30 microM of troglitazone caused a significant, dose-dependent reduction of cholesterol synthesis in both HepG2 and Caco-2 cells (P < 0.05). HepG2 and Caco-2 cells incubated with 10 or 30 microM of troglitazone had also lower mRNA concentrations and lower nuclear protein concentrations of SREBP-2 than untreated control cells (P < 0.05). mRNA concentrations of the SREBP-2 target genes HMG-CoA reductase and LDL receptor were also reduced in HepG2 and Caco-2 cells treated with 30 microM of troglitazone compared to control cells (P < 0.05). In conclusion, this study shows that PPAR gamma activation by troglitazone lowers the cholesterol synthesis in HepG2 and Caco-2 cells by reducing the concentration of nuclear SREBP-2 and successive downregulation of its target genes involved in cholesterol synthesis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Agregación Plaquetaria
/
Colesterol
/
Cromanos
/
Tiazolidinedionas
/
PPAR gamma
/
Proteína 2 de Unión a Elementos Reguladores de Esteroles
Límite:
Humans
Idioma:
En
Revista:
Exp Biol Med (Maywood)
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
/
MEDICINA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido