Identification of the human ApoAV gene as a novel ROR{alpha} target gene
- Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden)
Retinoic acid receptor-related orphan receptor-{alpha} (ROR{alpha}) (NR1F1) is an orphan nuclear receptor with a potential role in metabolism. Previous studies have shown that ROR{alpha} regulates transcription of the murine Apolipoprotein AI gene and human Apolipoprotein CIII genes. In the present study, we present evidence that ROR{alpha} also induces transcription of the human Apolipoprotein AV gene, a recently identified apolipoprotein associated with triglyceride levels. Adenovirus-mediated overexpression of ROR{alpha} increased the endogenous expression of ApoAV in HepG2 cells and ROR{alpha} also enhanced the activity of an ApoAV promoter construct in transiently transfected HepG2 cells. Deletion and mutation studies identified three AGGTCA motifs in the ApoAV promoter that mediate ROR{alpha} transactivation, one of which overlaps with a previously identified binding site for PPAR{alpha}. Together, these results suggest a novel mechanism whereby ROR{alpha} modulates lipid metabolism and implies ROR{alpha} as a potential target for the treatment of dyslipidemia and atherosclerosis.
- OSTI ID:
- 20709161
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 330, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.02.151; PII: S0006-291X(05)00429-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines
Effect of TNF{alpha} on activities of different promoters of human apolipoprotein A-I gene