Astaxanthin rich crude extract of Haematococcus pluvialis induces cytochrome P450 1A1 mRNA by activating aryl hydrocarbon receptor in rathepatoma H4IIE cells
Astaxanthin rich crude extract of Haematococcus pluvialis induces cytochrome P450 1A1 mRNA by activating aryl hydrocarbon receptor in rathepatoma H4IIE cells
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富含虾青素的雨生红球藻粗提物通过激活 Rathepatoma H4IIE 细胞中的芳基烃受体诱导细胞色素 P450 1A1 mRNA
DOI：
10.1016/j.foodchem.2011.07.050
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发表时间：
2011
期刊：
影响因子：
8.8
通讯作者：
大野円実
中科院分区：
文献类型：
--
作者：
佐藤正明;神田夏輝;樋口卓也;鈴木隆行;小西邦昭;吉岡孝高;三沢和彦;五神真;大野円実
叶黄素，虾青素(Ax)，强烈诱导大鼠和小鼠细胞色素P450(CYP)1A依赖的活性，通过增加Cyp1a1mRNA的转录而实现，其机制尚未确定。在这项研究中，我们研究了在H4IIE大鼠肝癌细胞中加入富含Ax的雨生红球菌粗提物对芳烃受体(AhR)相关事件的影响。雨生螺旋藻提取物(100Mol/L，17.6倍)可显著增加Cyp1a1mRNA的表达。雨生螺旋藻提取物作用6小时后，Cyp1a1基因的表达水平最高(25倍)，但暴露12小时和24小时后，Cyp1a1基因的诱导水平降低。绿色荧光蛋白标记的AhR在Ax作用10min后在COS-7细胞中被转位到细胞核。此外，含有Ax的雨生螺旋藻提取物在荧光素酶实验中激活了人的CYP1A1增强子区域，凝胶漂移试验表明，雨生螺旋藻提取物刺激的核蛋白可以与CYP1A1启动子中的外源反应元件(XRE)特异性地相互作用。综上所述，这些结果表明，雨生草提取物中所含的Ax可能通过激活和转位XRE结合形式的AhR而导致Cyp1a1 mRNA的诱导。
The xanthophyll, astaxanthin (Ax), strongly induces cytochrome P450 (CYP) 1A-dependent activity in rats and mice, via increased transcription of Cyp1a1 mRNA through an undetermined mechanism. In this study, we have investigated how aryl hydrocarbon receptor (AhR)-related events are affected by the addition of Ax-rich crude extract from Haematococcus pluvialis in H4IIE rat hepatoma cells. The expression of Cyp1a1 mRNA was significantly increased by exposure to H. pluvialis extract (100μmol/l, 17.6-fold). The highest level of Cyp1a1 mRNA was observed after a 6-h exposure to H. pluvialis extract (25-fold), but 12- and 24-h exposures resulted in lower levels of induction. Green fluorescence protein-tagged AhR was translocated into the nucleus in COS-7 cells after a 10min exposure to Ax. Moreover, H. pluvialis extract containing Ax activated the human CYP1A1 enhancer region in a luciferase assay, and a gel shift assay showed that nuclear proteins stimulated by H. pluvialis extract can interact specifically with xenobiotic responsive elements (XREs) in the CYP1A1 promoter. Together these results indicate the possibility that Ax, contained in H. pluvialis extract, caused the induction of Cyp1a1 mRNA through the activation and translocation of an XRE-binding form of AhR.