Title |
The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability
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Published in |
Frontiers in Pharmacology, September 2017
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DOI | 10.3389/fphar.2017.00596 |
Pubmed ID | |
Authors |
Limei Wang, Veronika Palme, Nicole Schilcher, Angela Ladurner, Elke H. Heiss, Herbert Stangl, Rudolf Bauer, Verena M. Dirsch, Atanas G. Atanasov |
Abstract |
We report increased cholesterol efflux from macrophages in the presence of falcarindiol, an important dietary constituent present in commonly used vegetables and medicinal plants. Falcarindiol (3-20 μM) increased cholesterol efflux from THP-1-derived macrophages. Western blot analysis showed an increased protein level of ABCA1 upon falcarindiol exposure. Quantitative real-time PCR revealed that also ABCA1 mRNA level rise with falcarindiol (10 μM) treatment. The effect of falcarindiol on ABCA1 protein as well as mRNA level were counteracted by co-treatment with BADGE, an antagonist of PPARγ. Furthermore, falcarindiol significantly inhibited ABCA1 protein degradation in the presence of cycloheximide. This post-translational regulation of ABCA1 by falcarindiol occurs most likely by inhibition of lysosomal cathepsins, resulting in decreased proteolysis and extended protein half-life of ABCA1. Taken together, falcarindiol increases ABCA1 protein level by two complementary mechanisms, i.e., promoting ABCA1 gene expression and inhibiting ABCA1 protein degradation, which lead to enhanced cholesterol efflux. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Switzerland | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 18 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 3 | 17% |
Researcher | 3 | 17% |
Lecturer > Senior Lecturer | 2 | 11% |
Student > Postgraduate | 2 | 11% |
Student > Bachelor | 1 | 6% |
Other | 5 | 28% |
Unknown | 2 | 11% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 5 | 28% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 17% |
Chemistry | 2 | 11% |
Immunology and Microbiology | 1 | 6% |
Agricultural and Biological Sciences | 1 | 6% |
Other | 2 | 11% |
Unknown | 4 | 22% |