| Autor: |
Medicia Kartawijaya, Hye Won Han, Yunhye Kim, Seung-Min Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Food & Nutrition Research, Vol 60, Iss 0, Pp 1-8 (2016) |
| Druh dokumentu: |
article |
| ISSN: |
1654-661X |
| DOI: |
10.3402/fnr.v60.31120 |
| Popis: |
Background: Genistein has been proved in vitro and in vivo to lower LDLR level. It is also widely consumed and implicated for its anti-atherogenic effects. However, the molecular mechanism by which genistein lowers the LDL level is still unknown. Objective: To understand the anti-atherogenic molecular mechanism of action, genistein was investigated for its impact on the expression of LDLR, the receptor for LDL cholesterol, and related signaling pathways in a human hepatoma cell line. Design: HepG2 cell was used for the experiments. Genistein with different concentrations was diluted in media and was incubated for 24 h or more as indicated. Protein levels were measured by western blotting, and mRNA expression was detected by RT-qPCR. Chromatin immunoprecipitation assay (CHIP) assay was used to determine protein binding levels, and luciferase assay was used to measure promoter activity. Result: Genistein increased the mRNA and protein levels of LDLR in a time-dependent manner. Genistein increased the transcriptional activity of the LDLR promoter containing the reporter gene (pLDLR-luc, −805 to +50). But the sterol regulatory element deletion mutant construct failed to be activated by genistein. Genistein increased the nuclear fraction of SREBP-2 and the DNA-binding activity of SREBP-2 to LDLR promoter, as assessed by CHIP. The genistein-phosphorylated JNK inhibitor (SP600126) abolished the genistein-stimulated levels of LDLR and the nuclear SREBP-2. The addition of cholesterol up to 5 µg/mL for 24 h did not affect the effect of genistein on LDLR protein expression. Even the addition of 40 µM genistein increased the cholesterol uptake by more than 10% in the human hepatoma cell line. Conclusion: Our data support the idea that genistein may have anti-atherogenic effects by activating JNK signals and SREBP-2 processing, which is followed by the upregulation of LDLR. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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