Academic Journal
Induction of the intestinal membrane transporters ABCA1 and ABCG8 by 27-hydroxycholesterol through a redox mechanism
| العنوان: | Induction of the intestinal membrane transporters ABCA1 and ABCG8 by 27-hydroxycholesterol through a redox mechanism |
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| المؤلفون: | Noemi Iaia, Valerio Leoni, Giuseppe Poli, Fiorella Biasi |
| المصدر: | Redox Experimental Medicine, Vol 2024, Iss 1, Pp 1-8 (2024) |
| بيانات النشر: | Bioscientifica, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Physiology LCC:Therapeutics. Pharmacology |
| مصطلحات موضوعية: | 27-hydroxycholesterol, abc transporters, abca1, abcg8, caco-2 cells, oxysterols, plant sterols, Physiology, QP1-981, Therapeutics. Pharmacology, RM1-950 |
| الوصف: | Objective: We tested the effect of 27-hydroxycholesterol (27OHC) on the expression and synthesis of two membrane transporters involved in sterols extrusion from the intestinal epithelium into the gut lumen: ATP-binding cassette A1 (ABCA1) and G8 (ABCG8). Special attention was given to ABCG8, a key player in the intestinal cell discharge of plant sterols. Methods: Differentiated CaCo-2 intestinal cells were supplemented with 27OHC, and added to the cell incubation medium at a final concentration of 1 or 5 μM. These 27OHC externally added amounts were proven to reach intracellular oxysterol levels within the range of those normally recovered in the human peripheral blood. Results: An up-regulation of the ABCA1 and ABCG8 mRNAs was observed in the CaCo-2 cells supplemented with 27OHC. Moreover, both 1 μM and 5 μM 27OHC induced a net, and steady, statistically significant, increase of both ABCA1 and ABCG8 protein levels. Of interest, the cellular pre-treatment with diphenylene iodonium, a selective inhibitor of NADPH oxidase, i.e. a major intracellular source of reactive oxygen species, fully inhibited the 27OHC enhancement of both ABCA1 and ABCG8 protein synthesis. Conclusion: This in vitro study shows for the first time that the addition of 27OHC to intestinal epithelial cells up-regulates ABCG8, the transporter discharging plant sterols into the gut lumen, besides confirming to induce ABCA1 as well. Importantly, the 27OHC-dependent up-regulation of the two transporters appears to involve a redox mechanism rather than the canonical liver-X-receptors-dependent pathway. Significance statement The 27OHC introduced with the diet might modulate the plant sterol extrusion in the gut, in parallel with that of cholesterol. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2755-158X |
| Relation: | https://rem.bioscientifica.com/view/journals/rem/2024/1/REM-24-0005.xml; https://doaj.org/toc/2755-158X |
| DOI: | 10.1530/REM-24-0005 |
| URL الوصول: | https://doaj.org/article/7d8b854bdc9c42b8b4ec255345fd2b62 |
| رقم الانضمام: | edsdoj.7d8b854bdc9c42b8b4ec255345fd2b62 |
| قاعدة البيانات: | Directory of Open Access Journals |
| تدمد: | 2755158X |
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| DOI: | 10.1530/REM-24-0005 |