Abstract
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.
Lind, Ulrika;
[1]
Nilsson, Tina;
[1]
McPheat, Jane;
[1]
Stroemstedt, Per-Erik;
[1]
Bamberg, Krister;
[1]
Balendran, Clare;
[1]
Kang, Daiwu
[1]
- Department of Molecular Pharmacology, AstraZeneca R and D Moelndal (Sweden)
Citation Formats
Lind, Ulrika, Nilsson, Tina, McPheat, Jane, Stroemstedt, Per-Erik, Bamberg, Krister, Balendran, Clare, and Kang, Daiwu.
Identification of the human ApoAV gene as a novel ROR{alpha} target gene.
United States: N. p.,
2005.
Web.
doi:10.1016/j.bbrc.2005.02.151.
Lind, Ulrika, Nilsson, Tina, McPheat, Jane, Stroemstedt, Per-Erik, Bamberg, Krister, Balendran, Clare, & Kang, Daiwu.
Identification of the human ApoAV gene as a novel ROR{alpha} target gene.
United States.
https://doi.org/10.1016/j.bbrc.2005.02.151
Lind, Ulrika, Nilsson, Tina, McPheat, Jane, Stroemstedt, Per-Erik, Bamberg, Krister, Balendran, Clare, and Kang, Daiwu.
2005.
"Identification of the human ApoAV gene as a novel ROR{alpha} target gene."
United States.
https://doi.org/10.1016/j.bbrc.2005.02.151.
@misc{etde_20709161,
title = {Identification of the human ApoAV gene as a novel ROR{alpha} target gene}
author = {Lind, Ulrika, Nilsson, Tina, McPheat, Jane, Stroemstedt, Per-Erik, Bamberg, Krister, Balendran, Clare, and Kang, Daiwu}
abstractNote = {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.}
doi = {10.1016/j.bbrc.2005.02.151}
journal = []
issue = {1}
volume = {330}
place = {United States}
year = {2005}
month = {Apr}
}
title = {Identification of the human ApoAV gene as a novel ROR{alpha} target gene}
author = {Lind, Ulrika, Nilsson, Tina, McPheat, Jane, Stroemstedt, Per-Erik, Bamberg, Krister, Balendran, Clare, and Kang, Daiwu}
abstractNote = {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.}
doi = {10.1016/j.bbrc.2005.02.151}
journal = []
issue = {1}
volume = {330}
place = {United States}
year = {2005}
month = {Apr}
}