LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL.
Lipids Health Dis
; 10: 134, 2011 Aug 05.
Article
en En
| MEDLINE
| ID: mdl-21819577
ABSTRACT
BACKGROUND:
The physiological regulation of hepatic apoE gene has not been clarified, although the expression of apoE in adipocytes and macrophages has been known to be regulated by LXR. METHODS ANDRESULTS:
We investigated the effect of TO901317, a LXR agonist, on hepatic apoE production utilizing HepG2 cells cultured in spheroid form, known to be more differentiated than HepG2 cells in monolayer culture. Spheroid HepG2 cells were prepared in alginate-beads. The secretions of albumin, apoE and apoA-I from spheroid HepG2 cells were significantly increased compared to those from monolayer HepG2 cells, and these increases were accompanied by increased mRNA levels of apoE and apoA-I. Several nuclear receptors including LXRα also became abundant in nuclear fractions in spheroid HepG2 cells. Treatment with TO901317 significantly increased apoE protein secretion from spheroid HepG2 cells, which was also associated with the increased expression of apoE mRNA. Separation of the media with FPLC revealed that the production of apoE-rich large HDL particles were enhanced even at low concentration of TO901317, and at higher concentration of TO901317, production of VLDL particles increased as well.CONCLUSIONS:
LXR activation enhanced the expression of hepatic apoE, together with the alteration of lipoprotein particles produced from the differentiated hepatocyte-derived cells. HepG2 spheroids might serve as a good model of well-differentiated human hepatocytes for future investigations of hepatic lipid metabolism.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Apolipoproteínas E
/
Regulación hacia Arriba
/
Esferoides Celulares
/
Hepatocitos
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Receptores Nucleares Huérfanos
/
Lipoproteínas HDL
/
Lipoproteínas VLDL
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Lipids Health Dis
Asunto de la revista:
BIOQUIMICA
/
METABOLISMO
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón