期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms23095243
关键词
antioxidant effect; arsenite; CRISPR-Cas9; dietary phytochemicals; equol; Keap1-Nrf2 pathway; soy-derived isoflavones; zebrafish
资金
- Takano Life Science Research Foundation
- Mishima Kaiun Memorial Foundation
- Japan Food Chemical Research Foundation
- Food Science Institute Foundation
- KOSE Cosmetology Research Foundation
- MEXT/JSPS KAKENHI [JP21J11172]
The antioxidant effects of seven isoflavones were evaluated using a zebrafish assay system. Among these, equol showed strong antioxidant effects, independent of the Keap1-Nrf2 pathway. Gene expression analysis revealed that equol may upregulate antioxidant activity in zebrafish through a different mechanism.
Antioxidant effects of soy-derived isoflavones are predicted to be mediated by the Keap1-Nrf2 pathway. Recently, we constructed an assay system to evaluate the antioxidant effects of dietary phytochemicals in zebrafish and revealed a relationship between these effects and the Keap1-Nrf2 pathway. In this study, we used this system to examine the antioxidant effects of seven isoflavones. Among those seven, equol showed strong antioxidant effects when arsenite was used as an oxidative stressor. The antioxidant effect of equol was also shown in Nrf2-mutant zebrafish nfe2l2a(fh318), suggesting that this effect was not mediated by the Keap1-Nrf2 pathway. To elucidate this unidentified mechanism, the gene expression profiles of equol-treated larvae were analyzed using RNA-seq and qRT-PCR, while no noticeable changes were detected in the expression of genes related to antioxidant effects, except weak induction of Nrf2 target genes. Because nfe2l2a(fh318) is an amino acid-substitution mutant (Arg485Lue), we considered that the antioxidant effect of equol in this mutant might be due to residual Nrf2 activity. To examine this possibility, we generated an Nrf2-knockout zebrafish nfe2l2a(it321) using CRISPR-Cas9 and analyzed the antioxidant effect of equol. As a result, equol showed strong antioxidant effects even in Nrf2-knockout larvae, suggesting that equol indeed upregulates antioxidant activity in zebrafish in an Nrf2-independent manner.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据