Alpha-crystallin is a target gene of the farnesoid X-activated receptor in human livers.
J Biol Chem
; 280(36): 31792-800, 2005 Sep 09.
Article
en En
| MEDLINE
| ID: mdl-16012168
Alpha-crystallins comprise 35% of soluble proteins in the ocular lens and possess chaperone-like functions. Furthermore, the alphaA subunit (alphaA-crystallin) of alpha crystallin is thought to be "lens-specific" as only very low levels of expression were detected in a few non-lenticular tissues. Here we report that human alphaA-crystallin is expressed in human livers and is regulated by farnesoid X-activated receptor (FXR) in response to FXR agonists. AlphaA-crystallin was identified in a microarray screen as one of the most highly induced genes after treatment of HepG2 cells with the synthetic FXR ligand GW4064. Northern blot and quantitative real-time PCR analyses confirmed that alphaA-crystallin expression was induced in HepG2-derived cell lines and human primary hepatocytes and hepatic stellate cells in response to either natural or synthetic FXR ligands. Transient transfection studies and electrophoretic mobility shift assays revealed a functional FXR response element located in intron 1 of the human alphaA-crystallin gene. Importantly, immunohistochemical staining of human liver sections showed increased alphaA-crystallin expression in cholangiocytes and hepatocytes. As a member of the small heat shock protein family possessing chaperone-like activity, alphaA-crystallin may be involved in protection of hepatocytes from the toxic effects of high concentrations of bile acids, as would occur in disease states such as cholestasis.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Regulación de la Expresión Génica
/
Alfa-Cristalinas
/
Proteínas de Unión al ADN
/
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Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos