NO-1886 up-regulates Niemann-Pick C1 protein (NPC1) expression through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells.
Cardiovasc Drugs Ther
; 23(3): 199-206, 2009 Jun.
Article
em En
| MEDLINE
| ID: mdl-19229602
ABSTRACT
BACKGROUND:
The Niemann-Pick C1 (NPC1) protein regulates the transport of cholesterol from late endosomes/lysosomes to other compartments responsible for maintaining intracellular cholesterol homeostasis. Liver X receptors (LXRs) operate as cholesterol sensors which may protect from cholesterol overload by increasing the amount of free cholesterol in the plasma membrane through inducing NPC1 expression. NO-1886 has been proven to be highly effective at increasing liver X receptor alpha expression and promoting cellular cholesterol efflux. In this study, the effects of NO-1886 on NPC1 expression were investigated in THP-1 macrophage-derived foam cells. METHODS ANDRESULTS:
Results showed that NO-1886 markedly increased expression of NPC1 at both mRNA level and protein level in a dose-dependent and time-dependent manner. Cellular cholesterol content was decreased while cholesterol efflux was increased by NO-1886 treatment. In addition, LXR alpha was also up-regulated by NO-1886 treatment. And LXR alpha small interfering RNA completely abolished the promotion effect which was induced by NO-1886.CONCLUSION:
These results provide evidence that NO-1886 up-regulates expression of NPC1 through LXR alpha pathway in THP-1 macrophage- derived foam cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
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Benzamidas
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Glicoproteínas de Membrana
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Proteínas de Transporte
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Receptores Citoplasmáticos e Nucleares
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Proteínas de Ligação a DNA
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Células Espumosas
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Hipolipemiantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article