The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability
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 incr...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-09-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2017.00596/full |
| _version_ | 1819104724572438528 |
|---|---|
| author | Limei Wang Limei Wang Veronika Palme Nicole Schilcher Angela Ladurner Elke H. Heiss Herbert Stangl Rudolf Bauer Verena M. Dirsch Atanas G. Atanasov Atanas G. Atanasov |
| author_facet | Limei Wang Limei Wang Veronika Palme Nicole Schilcher Angela Ladurner Elke H. Heiss Herbert Stangl Rudolf Bauer Verena M. Dirsch Atanas G. Atanasov Atanas G. Atanasov |
| author_sort | Limei Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T02:10:54Z |
| format | Article |
| id | doaj.art-28ec044aadc84ed69029636e5400f358 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T02:10:54Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-28ec044aadc84ed69029636e5400f3582022-12-21T18:42:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-09-01810.3389/fphar.2017.00596286816The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein StabilityLimei Wang0Limei Wang1Veronika Palme2Nicole Schilcher3Angela Ladurner4Elke H. Heiss5Herbert Stangl6Rudolf Bauer7Verena M. Dirsch8Atanas G. Atanasov9Atanas G. Atanasov10Department of Pharmacognosy, University of ViennaVienna, AustriaDepartment of Pharmacology, School of Pharmacy, Qingdao UniversityQingdao, ChinaDepartment of Pharmacognosy, University of ViennaVienna, AustriaDepartment of Pharmacognosy, University of ViennaVienna, AustriaDepartment of Pharmacognosy, University of ViennaVienna, AustriaDepartment of Pharmacognosy, University of ViennaVienna, AustriaCenter for Pathobiochemistry and Genetics, Institute of Medical Chemistry, Medical University of ViennaVienna, AustriaDepartment of Pharmacognosy, Institute of Pharmaceutical Sciences, Karl-Franzens-University GrazGraz, AustriaDepartment of Pharmacognosy, University of ViennaVienna, AustriaDepartment of Pharmacognosy, University of ViennaVienna, AustriaDepartment of Molecular Biology, Institute of Genetics and Animal Breeding of the Polish Academy of SciencesLesznowola, PolandWe 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.http://journal.frontiersin.org/article/10.3389/fphar.2017.00596/fullfalcarindiolcholesterol effluxABCA1protein degradationPPARγ |
| spellingShingle | Limei Wang Limei Wang Veronika Palme Nicole Schilcher Angela Ladurner Elke H. Heiss Herbert Stangl Rudolf Bauer Verena M. Dirsch Atanas G. Atanasov Atanas G. Atanasov The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability Frontiers in Pharmacology falcarindiol cholesterol efflux ABCA1 protein degradation PPARγ |
| title | The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability |
| title_full | The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability |
| title_fullStr | The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability |
| title_full_unstemmed | The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability |
| title_short | The Dietary Constituent Falcarindiol Promotes Cholesterol Efflux from THP-1 Macrophages by Increasing ABCA1 Gene Transcription and Protein Stability |
| title_sort | dietary constituent falcarindiol promotes cholesterol efflux from thp 1 macrophages by increasing abca1 gene transcription and protein stability |
| topic | falcarindiol cholesterol efflux ABCA1 protein degradation PPARγ |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2017.00596/full |
| work_keys_str_mv | AT limeiwang thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT limeiwang thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT veronikapalme thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT nicoleschilcher thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT angelaladurner thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT elkehheiss thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT herbertstangl thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT rudolfbauer thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT verenamdirsch thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT atanasgatanasov thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT atanasgatanasov thedietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT limeiwang dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT limeiwang dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT veronikapalme dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT nicoleschilcher dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT angelaladurner dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT elkehheiss dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT herbertstangl dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT rudolfbauer dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT verenamdirsch dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT atanasgatanasov dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability AT atanasgatanasov dietaryconstituentfalcarindiolpromotescholesteroleffluxfromthp1macrophagesbyincreasingabca1genetranscriptionandproteinstability |