Inhibition of LXRalpha signaling by vitamin D receptor: possible role of VDR in bile acid synthesis.
Biochem Biophys Res Commun
; 351(1): 176-84, 2006 Dec 08.
Article
en En
| MEDLINE
| ID: mdl-17054913
The expression of cholesterol 7alpha-hydroxylase (CYP7alpha), the rate-limiting enzyme in the catabolism of cholesterol to bile acid, is stimulated by oxysterol receptor, liver X receptor alpha (LXRalpha) and negatively regulated by a bile acid receptor, farnesoid X receptor. In the current study, we demonstrated that 1,25-(OH)(2)D3 blunted the LXRalpha-mediated induction of CYP7alpha mRNA in H4IIE rat hepatoma cells. In co-transfection experiments in HepG2 cells, VDR repressed the activity of rat CYP7alpha promoter in a ligand-dependent manner through inhibition of LXRalpha signaling. We also confirmed the ability of VDR to repress LXRalpha transcriptional activation using a synthetic LXRalpha responsive reporter. Deletion analyses revealed that the ligand-binding domain of VDR was required for the suppression and the DNA-binding domain was dispensable. Given the fact that VDR can be activated by the secondary bile acid as well as 1,25-(OH)(2)D3, the crosstalk between LXRalpha and VDR signaling in regulation of bile acid metabolism provides a possible contribution of VDR to modulate bile acid and cholesterol homeostasis, and highlights a physiological function of VDR beyond calcium metabolism in the body.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Calcitriol
/
Colesterol 7-alfa-Hidroxilasa
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Transducción de Señal
/
Receptores Citoplasmáticos y Nucleares
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Receptores de Calcitriol
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Carcinoma Hepatocelular
/
Proteínas de Unión al ADN
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2006
Tipo del documento:
Article
País de afiliación:
China