β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells
Xia-qing Gao,1,2 Yan-fang Li,1,2 Zhi-li Jiang1,2 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People’s Republic of China Objective: The aim of this study was to explore the effects of...
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| Format: | Article |
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Dove Medical Press
2017-03-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/beta3-adrenoceptor-activation-upregulates-apolipoprotein-a-i-expressio-peer-reviewed-article-DDDT |
| _version_ | 1818230660419026944 |
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| author | Gao XQ Li YF Jiang ZL |
| author_facet | Gao XQ Li YF Jiang ZL |
| author_sort | Gao XQ |
| collection | DOAJ |
| description | Xia-qing Gao,1,2 Yan-fang Li,1,2 Zhi-li Jiang1,2 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People’s Republic of China Objective: The aim of this study was to explore the effects of β3-adrenoceptor (β3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. Materials and methods: HepG2 cells were cultured and treated with the β3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and β3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol content of the foam cells was also measured, and the cholesterol efflux from the macrophages was examined by determining 3H-labeled cholesterol levels. Expression of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam cells was also assessed. Results: β3-AR activation increased ApoA-I expression in both the HepG2 cells and the supernatants; PPARγ expression was upregulated, but PPARα expression was not. Treatment with GW9662 abolished the increased expression of ApoA-I induced by the β3-AR agonist. The HepG2 cell supernatants decreased the lipid accumulation and increased the cholesterol efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1 expression, increased in the macrophage foam cells treated with BRL37344-treated HepG2 cell supernatants. Conclusion: Activation of β3-AR in HepG2 cells upregulates ApoA-I expression, which might further promote cholesterol efflux from macrophage foam cells. PPARγ might be required for the induction of ApoA-I expression. Keywords: β3-adrenoceptor, HepG2 cell, macrophage foam cell, atherosclerosis, cholesterol efflux, reverse cholesterol transport |
| first_indexed | 2024-12-12T10:38:02Z |
| format | Article |
| id | doaj.art-3bd629e99b9340b29ae836a02196e857 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-12T10:38:02Z |
| publishDate | 2017-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-3bd629e99b9340b29ae836a02196e8572022-12-22T00:27:08ZengDove Medical PressDrug Design, Development and Therapy1177-88812017-03-01Volume1161762731682β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cellsGao XQLi YFJiang ZLXia-qing Gao,1,2 Yan-fang Li,1,2 Zhi-li Jiang1,2 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, 2Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, People’s Republic of China Objective: The aim of this study was to explore the effects of β3-adrenoceptor (β3-AR) activation on HepG2 cells and its influence on cholesterol efflux from macrophage foam cells. Materials and methods: HepG2 cells were cultured and treated with the β3-AR agonist, BRL37344, and antagonist, SR52390A, and the expression of apolipoprotein (Apo) A-I, ApoA-II, ApoB, and β3-AR in the supernatants and cells was determined. The expression of peroxisome proliferator-activated receptor (PPAR) γ and PPARα in the HepG2 cells was also assessed. Next, using the RAW264.7 macrophage foam cell model, we also assessed the influence of the HepG2 cell supernatants on lipid efflux. The cholesterol content of the foam cells was also measured, and the cholesterol efflux from the macrophages was examined by determining 3H-labeled cholesterol levels. Expression of ATP-binding cassette transporter (ABC) A1 and ABCG1 of the macrophage foam cells was also assessed. Results: β3-AR activation increased ApoA-I expression in both the HepG2 cells and the supernatants; PPARγ expression was upregulated, but PPARα expression was not. Treatment with GW9662 abolished the increased expression of ApoA-I induced by the β3-AR agonist. The HepG2 cell supernatants decreased the lipid accumulation and increased the cholesterol efflux from the macrophage foam cells. ABCA1 expression, but not ABCG1 expression, increased in the macrophage foam cells treated with BRL37344-treated HepG2 cell supernatants. Conclusion: Activation of β3-AR in HepG2 cells upregulates ApoA-I expression, which might further promote cholesterol efflux from macrophage foam cells. PPARγ might be required for the induction of ApoA-I expression. Keywords: β3-adrenoceptor, HepG2 cell, macrophage foam cell, atherosclerosis, cholesterol efflux, reverse cholesterol transporthttps://www.dovepress.com/beta3-adrenoceptor-activation-upregulates-apolipoprotein-a-i-expressio-peer-reviewed-article-DDDTβ3-AdrenoceptorHepG2 cellmacrophage foam cellatherosclerosischolesterol effluxreverse cholesterol transport |
| spellingShingle | Gao XQ Li YF Jiang ZL β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells Drug Design, Development and Therapy β3-Adrenoceptor HepG2 cell macrophage foam cell atherosclerosis cholesterol efflux reverse cholesterol transport |
| title | β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells |
| title_full | β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells |
| title_fullStr | β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells |
| title_full_unstemmed | β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells |
| title_short | β3-Adrenoceptor activation upregulates apolipoprotein A-I expression in HepG2 cells, which might further promote cholesterol efflux from macrophage foam cells |
| title_sort | beta 3 adrenoceptor activation upregulates apolipoprotein a i expression in hepg2 cells which might further promote cholesterol efflux from macrophage foam cells |
| topic | β3-Adrenoceptor HepG2 cell macrophage foam cell atherosclerosis cholesterol efflux reverse cholesterol transport |
| url | https://www.dovepress.com/beta3-adrenoceptor-activation-upregulates-apolipoprotein-a-i-expressio-peer-reviewed-article-DDDT |
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