Tanshindiol C inhibits oxidized low-density lipoprotein induced macrophage foam cell formation via a peroxiredoxin 1 dependent pathway
| Autor: | Yuyu Yang, Ping Li, Lin An, Jun Chen, Xuewen Hu, Ping Zhou, Li-Ying Peng, Yong Xu, Li Xueyan, Ning-Yuan Sun |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Salvia miltiorrhiza Peroxiredoxin 1 Mice 03 medical and health sciences Downregulation and upregulation Animals Humans Molecular Biology Cells Cultured Foam cell biology Sirtuin 1 Activator (genetics) Chemistry Peroxiredoxins Atherosclerosis Cell biology Lipoproteins LDL Mice Inbred C57BL HEK293 Cells 030104 developmental biology ABCA1 Macrophages Peritoneal biology.protein Molecular Medicine lipids (amino acids peptides and proteins) Diterpenes Intracellular ATP Binding Cassette Transporter 1 Drugs Chinese Herbal Foam Cells Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1864:882-890 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2017.12.033 |
| Popis: | NF-E2-related factor 2 (Nrf2) has been shown to be protective in atherosclerosis. The loss of Nrf2 in macrophages enhances foam cell formation and promotes early atherogenesis. Tanshindiol C (Tan C) is isolated from the root of Salvia miltiorrhiza Bge., a traditional Chinese medicine that has been used for the treatment of several cardiovascular diseases for many years. This study was aimed to test the potential role of Tan C against macrophage foam cell formation and to explore the underlying mechanism. Firstly, we observed that Tan C markedly suppressed oxidized low-density lipoprotein (oxLDL) induced macrophage foam cell formation. Then, we found that Tan C was an activator of both Nrf2 and Sirtuin 1 (Sirt1) in macrophages. Nrf2 and Sirt1 synergistically activated the transcription of anti-oxidant peroxiredoxin 1 (Prdx1) after Tan C treatment. More important, we demonstrated that silencing of Prdx1 promoted oxLDL-induced macrophage foam cell formation. Prdx1 upregulated adenosine triphosphate-binding cassette (ABC) transporter A1 (ABCA1) expression and decreased intracellular lipid accumulation. Furthermore, Tan C ameliorated oxLDL induced macrophage foam cell formation in a Prdx1-dependent manner. These observations suggest that Tan C protects macrophages from oxLDL induced foam cell formation via activation of Prdx1/ABCA1 signaling and that Prdx1 may be a novel target for therapeutic intervention of atherosclerosis. |
| Databáze: | OpenAIRE |
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