RRC ID 74529
著者 Ibata T, Lyu J, Imachi H, Fukunaga K, Sato S, Kobayashi T, Saheki T, Yoshimura T, Murao K.
タイトル Effects of 2-Methoxyestradiol, a Main Metabolite of Estradiol on Hepatic ABCA1 Expression in HepG2 Cells.
ジャーナル Nutrients
Abstract ATP-binding cassette transporter A1 (ABCA1) is a key regulator of lipid efflux, and the absence of ABCA1 induces hepatic lipid accumulation, which is one of the major causes of fatty liver. 2-Methoxyestradiol (2-ME2) has been demonstrated to protect against fatty liver. In this study, we investigated the effects of 2-ME2 on the hepatic lipid content and ABCA1 expression. We found that 2-ME2 dose-dependently increased ABCA1 expression, and therefore, the lipid content was significantly decreased in HepG2 cells. 2-ME2 enhanced the ABCA1 promoter activity; however, this effect was reduced after the inhibition of the PI3K pathway. The overexpression of Akt or p110 induced ABCA1 promoter activity, while dominant-negative Akt diminished the ability of 2-ME2 on ABCA1 promoter activity. Further, 2-ME2 stimulated the rapid phosphorylation of Akt and FoxO1 and reduced the nuclear accumulation of FoxO1. Chromatin immunoprecipitation confirmed that FoxO1 bonded to the ABCA1 promoter region. The binding was reduced by 2-ME2, which facilitated ABCA1 gene transcription. Furthermore, mutating FoxO1-binding sites in the ABCA1 promoter region or treatment with FoxO1-specific siRNA disrupted the effect of 2-ME2 on ABCA1 expression. All of our results demonstrated that 2-ME2 might upregulate ABCA1 expression via the PI3K/Akt/FoxO1 pathway, which thus reduces the lipid content in hepatocytes.
巻・号 14(2)
公開日 2022-1-11
DOI 10.3390/nu14020288
PII nu14020288
PMID 35057469
PMC PMC8779252
MeSH 2-Methoxyestradiol / pharmacology* ATP Binding Cassette Transporter 1 / drug effects* Fatty Liver / metabolism Hep G2 Cells Hepatocytes / metabolism Humans Lipid Metabolism / drug effects* Liver / metabolism Signal Transduction / drug effects
IF 4.546
リソース情報
ヒト・動物細胞 Hep G2