Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes
Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes
复制标题
姜黄素通过协调原代小鼠肝细胞中胞苷脱氨基与尿苷编辑体成分的表达来调节载脂蛋白 B mRNA 编辑
DOI：
10.4196/kjpp.2019.23.3.181
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发表时间：
2019-05-01
影响因子：
2
通讯作者：
Tian，Nan
中科院分区：
文献类型：
--
作者：
He，Pan;Tian，Nan
姜黄素是姜黄的有效成分，可通过不同途径降低血浆低密度脂蛋白浓度。我们首次报道了姜黄素通过改善大鼠原代肝细胞载脂蛋白B(ApoB)的mRNA编辑而显示出降胆固醇的特性。然而，姜黄素在apoB mRNA编辑调控中的作用尚不清楚。因此，我们研究了姜黄素对apoB基因胞苷脱氨基为尿苷(C-to-U)编辑小体多种编辑成分表达的影响。结果表明，50µM姜黄素可使小鼠原代肝细胞apoB基因编码量从5.13%~8.05%增加到27.63%~35.61%，并显著提高核心成分apoB编辑催化多肽-1(APOBEC-1)、APOBEC-1互补因子(ACF)和RNA结合基序蛋白-47(RBM47)的水平，抑制抑制成分甘氨酸-精氨酸-酪氨酸-富含RNA的结合蛋白的水平。此外，siRNA介导的APOBEC-1、ACF和RBM47基因敲除显著减少了50µM姜黄素增加的apoB RNA编辑。这些发现表明，姜黄素通过协调原代肝细胞中编辑小体的多个编辑成分来调节apoB mRNA的编辑。我们的数据为姜黄素用于治疗预防动脉粥样硬化提供了证据。
Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with 50 µM curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%–8.05% to 27.63%–35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by 50 µM curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the editosome in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.